Lisinopril and Hydrochlorothiazide

Description

Lisinopril is chemically described as (S)-1-N2-(1-carboxy-3-phenylpropyl)-L-lysyl-L-proline dihydrate, with an empirical formula of C21H31N3O5 • 2H2O. It appears as a white to off-white, crystalline powder and has a molecular weight of 441.52. Lisinopril 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. This compound is a white, or practically white, crystalline powder with a molecular weight of 297.73. Hydrochlorothiazide is slightly soluble in water and freely soluble in sodium hydroxide solution.

Lisinopril and hydrochlorothiazide tablets, USP, are formulated for oral use in strengths of 10 mg/12.5 mg, 20 mg/12.5 mg, and 20 mg/25 mg. The inactive ingredients in 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 effectively lower blood pressure. The reduction of blood pressure is associated with a decreased risk of both fatal and non-fatal cardiovascular events, particularly strokes and myocardial infarctions.

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

Clinical evidence from randomized controlled trials has demonstrated that various antihypertensive agents can significantly reduce cardiovascular morbidity and mortality, with blood pressure reduction being a key factor in these outcomes. The most substantial 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 linked to 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 different populations, with patients at higher baseline risk—such as those with diabetes or hyperlipidemia—experiencing greater absolute benefits.

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

Dosage and Administration

Lisinopril may be administered as monotherapy in once-daily doses ranging from 10 mg to 80 mg. Hydrochlorothiazide can be prescribed as monotherapy at daily doses between 12.5 mg and 50 mg.

For patients requiring combination therapy, 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 monotherapy, healthcare professionals may consider switching to lisinopril and hydrochlorothiazide tablets at dosages of either 10 mg/12.5 mg or 20 mg/12.5 mg.

Further increases in the dosage of either component may be warranted based on the clinical response of the patient. It is important to note that the hydrochlorothiazide dose should generally not be increased until a period of 2 to 3 weeks has elapsed. Dosages exceeding 80 mg of lisinopril and 50 mg of hydrochlorothiazide are not recommended.

The combination of lisinopril and hydrochlorothiazide may be used as a substitute for the titrated individual components. Additionally, usual regimens of therapy with lisinopril and hydrochlorothiazide tablets do not require adjustment in patients with a creatinine clearance greater than 30 mL/min/1.73 m², corresponding to a serum creatinine level of 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 monitor for these reactions closely.

Angioedema Angioedema, which can occur in the head and neck region, has been reported rarely but may arise at any point during treatment. Should angioedema occur, lisinopril must be discontinued immediately, and appropriate therapy should be initiated. Additionally, intestinal angioedema has been documented in patients treated with ACE inhibitors, with symptoms resolving upon cessation of the medication.

Desensitization Reactions Life-threatening anaphylactoid reactions have been observed in patients undergoing desensitization treatment while on ACE inhibitors. Caution is advised in these situations.

Hypotension Excessive hypotension may occur, particularly in patients who are salt or volume-depleted. Therefore, therapy should be initiated under close medical supervision in individuals with severe congestive heart failure to mitigate this risk.

Neutropenia and Agranulocytosis Rare instances of neutropenia and bone marrow depression have been reported. It is recommended that periodic monitoring of white blood cell counts be considered, especially in patients with collagen vascular disease or renal disease.

Hepatic Failure ACE inhibitors have been associated with a syndrome that can progress to fulminant hepatic necrosis and potentially result in death. If jaundice or significant elevations in hepatic enzymes are observed, discontinuation of the medication is warranted.

General Precautions Caution is advised when prescribing lisinopril to patients with aortic stenosis or hypertrophic cardiomyopathy due to potential obstruction in the left ventricular outflow tract. Changes in renal function may occur; therefore, renal function should be monitored during the initial weeks of therapy. Additionally, serum potassium levels should be monitored, particularly in patients with renal insufficiency or those on potassium-sparing diuretics. A persistent nonproductive cough may develop but typically resolves after discontinuation of therapy.

Surgery and Anesthesia Lisinopril may inhibit angiotensin II formation during major surgical procedures or anesthesia, which could lead to hypotension.

Laboratory Tests Periodic assessment of serum electrolytes is recommended to detect potential electrolyte imbalances. Furthermore, evaluation of renal function should be included in the assessment of hypertensive patients.

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

Discontinuation in Pregnancy Lisinopril and hydrochlorothiazide tablets should be discontinued as soon as pregnancy is detected, and the patient should contact their healthcare provider for further guidance.

Side Effects

Adverse reactions associated with the use of PRINZIDE have been observed in clinical trials and postmarketing experiences. These reactions can be categorized into common and additional adverse reactions, as well as serious warnings.

Common adverse reactions occurring in approximately 1% or more of patients include dizziness (7.5%), headache (5.2%), cough (3.9%), fatigue (3.7%), orthostatic effects (3.2%), 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%).

Additional adverse reactions reported include a variety of symptoms across different systems. Body as a whole reactions include chest pain, abdominal pain, syncope, chest discomfort, fever, trauma, and viral infections. Cardiovascular effects may involve palpitations and orthostatic hypotension. Digestive system reactions can include gastrointestinal cramps, dry mouth, constipation, and heartburn. Musculoskeletal complaints may consist of back pain, shoulder pain, knee pain, back strain, myalgia, and foot pain. Nervous and psychiatric effects include decreased libido, vertigo, depression, and somnolence. Respiratory issues may manifest as common cold, nasal congestion, influenza, bronchitis, pharyngeal pain, dyspnea, pulmonary congestion, chronic sinusitis, allergic rhinitis, and pharyngeal discomfort. Skin reactions can involve flushing, pruritus, skin inflammation, and diaphoresis. Special senses may be affected by blurred vision, tinnitus, and otalgia, while urogenital reactions may include urinary tract infections.

Serious warnings include the risk of angioedema, which has been reported more frequently in Black patients compared to non-Black patients. Angioedema associated with laryngeal edema can be fatal; therefore, if symptoms occur, treatment with PRINZIDE should be discontinued immediately, and appropriate therapy should be initiated. 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 patients. Additionally, a persistent nonproductive cough has been documented with all ACE inhibitors, resolving upon discontinuation of therapy.

Specific 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 complications can 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. Special senses may be affected by xanthopsia, and hypersensitivity reactions can include purpura, photosensitivity, urticaria, necrotizing angiitis, respiratory distress (including pneumonitis and pulmonary edema), and anaphylactic reactions.

It is important to note that 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. Rare cases of neutropenia and bone marrow depression have also been reported. Furthermore, ACE inhibitors have been linked to a syndrome that may begin with cholestatic jaundice or hepatitis and can progress to fulminant hepatic necrosis, occasionally resulting in death.

Drug Interactions

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

• NSAIDs: Co-administration of NSAIDs with lisinopril can result in renal function deterioration, particularly in elderly or volume-depleted patients. Renal function should be closely monitored, as the antihypertensive effect of lisinopril may also be diminished by NSAIDs.

• 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 alterations in renal function. It is recommended to avoid this combination.

• Aliskiren: In diabetic patients, the coadministration of aliskiren with lisinopril is contraindicated, particularly in those with renal impairment (GFR <60 ml/min).

• Potassium-Sparing Diuretics and Supplements: Lisinopril may elevate serum potassium levels when used alongside potassium-sparing diuretics or potassium supplements. Regular monitoring of serum potassium is advised.

• Lithium: The risk of lithium toxicity is heightened when lisinopril is used concurrently. Monitoring of serum lithium levels is essential.

• Angioedema Risk: Patients on ACE inhibitors, including lisinopril, who are also taking mTOR inhibitors or neprilysin inhibitors may have an increased risk of angioedema.

• Gold Injectable Products: Rare nitritoid reactions, characterized by flushing and hypotension, have been reported with the use of injectable gold in conjunction with lisinopril.

Pharmacokinetic Interactions:

• Hydrochlorothiazide: The use of hydrochlorothiazide may lead to several interactions:

  • Alcohol, barbiturates, or narcotics can enhance the risk of orthostatic hypotension.

  • Antidiabetic medications may require dosage adjustments when used with hydrochlorothiazide.

  • Other antihypertensive agents may have an additive effect, necessitating careful monitoring of blood pressure.

  • Cholestyramine and colestipol resins can significantly impair the absorption of hydrochlorothiazide, potentially reducing its efficacy.

  • Corticosteroids may exacerbate electrolyte depletion, particularly hypokalemia, when used concurrently.

• Lithium and Diuretics: The combination of lithium with diuretics is generally discouraged due to the risk of toxicity; renal clearance should be monitored closely.

• NSAIDs and Thiazide Diuretics: The effectiveness of thiazide diuretics may be diminished by NSAIDs, which necessitates close monitoring of the patient's response to treatment.

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

Pediatric patients, particularly neonates with a history of in utero exposure to lisinopril and hydrochlorothiazide tablets, require careful monitoring. In cases of oliguria or hypotension, it is essential to provide support for blood pressure and renal perfusion. Interventions such as exchange transfusions or dialysis may be necessary to address hypotension and manage impaired renal function. Lisinopril, which is known to cross the placenta, has been effectively removed from neonatal circulation through peritoneal dialysis, demonstrating some clinical benefit. Although theoretically, exchange transfusion may also facilitate the removal of lisinopril, there is currently no clinical experience to support this procedure.

Geriatric Use

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

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

A multiple-dose pharmacokinetic study comparing elderly and young hypertensive patients revealed that the area under the plasma concentration time curve (AUC) increased approximately 120% for lisinopril and approximately 80% for hydrochlorothiazide in older patients. This finding underscores the importance of careful monitoring and potential dose adjustments in the elderly population.

Given that this drug is substantially excreted by the kidneys, the risk of toxic reactions may be heightened in patients with impaired renal function. As elderly patients are more likely to experience decreased renal function, careful consideration should be given to dose selection. Therefore, the evaluation of hypertensive patients should always include an assessment of renal function 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. The use of Lisinopril during the second and third trimesters can lead to serious injury or death of the developing fetus. Clinical evidence indicates adverse effects on fetal development associated with Lisinopril administration during pregnancy.

Hydrochlorothiazide is also not recommended for use during pregnancy, as it may pose a risk of fetal harm. While there are no established safety concerns regarding the use of Hydrochlorothiazide in pregnant women, it should be administered with caution. Both Lisinopril and Hydrochlorothiazide should be avoided in pregnant patients unless the potential benefits outweigh the potential risks to the fetus.

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 another study indicating that lisinopril was present in rat milk at levels comparable 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 in individuals with severe renal disease. The cumulative effects of thiazides can develop in patients with reduced kidney function, necessitating careful monitoring.

In the context of angiotensin converting enzyme inhibitors, such as lisinopril, there is a potential risk of neutropenia and agranulocytosis, particularly in patients with renal impairment or those with concurrent collagen vascular diseases. Although clinical trial data for lisinopril are insufficient to definitively rule out a similar risk as seen with captopril, rare cases of neutropenia and bone marrow depression have been reported. Therefore, periodic monitoring of white blood cell counts is advisable for patients with both collagen vascular disease and renal disease.

Excessive hypotension is a concern in patients with renal impairment, especially in those who are salt/volume-depleted, such as individuals receiving vigorous diuretic therapy or those on dialysis. In patients with severe congestive heart failure, whether or not they have associated renal insufficiency, excessive hypotension may occur and could lead to oliguria, progressive azotemia, and, in rare cases, acute renal failure or death. Consequently, therapy should be initiated under close medical supervision, with careful monitoring during the first two weeks of treatment and following any dose adjustments of lisinopril or diuretics.

Additionally, hydrochlorothiazide should be used cautiously in patients with impaired hepatic function or progressive liver disease, as even minor alterations in fluid and electrolyte balance may precipitate hepatic coma.

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 underlying mechanism of this syndrome remains unclear. Therefore, patients receiving ACE inhibitors who develop jaundice or significant elevations in hepatic enzymes should 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 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 using established medical procedures.

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 studies involving lisinopril and hydrochlorothiazide. In non-teratogenic assessments, 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, 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. Additionally, no mutagenic effects were observed in a forward mutation assay using Chinese hamster lung cells. The combination also 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 both in vitro tests with Chinese hamster ovary cells and in vivo studies 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, based on body surface area. Lisinopril was consistently negative in various mutagenicity assays, including the Ames test and the forward mutation assay, and did not produce single strand DNA breaks or chromosomal aberrations.

Hydrochlorothiazide was evaluated in two-year feeding studies conducted by the National Toxicology Program (NTP), which found no evidence of 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). However, the NTP did report equivocal evidence for hepatocarcinogenicity in male mice. Hydrochlorothiazide was also not genotoxic in in vitro assays, including the Ames test and tests for chromosomal aberrations in Chinese hamster ovary cells, as well as 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. Angioedema associated with laryngeal edema may be fatal. In cases where angioedema of the face, extremities, lips, tongue, glottis, and/or larynx occurs, discontinuation of PRINZIDE and immediate initiation of appropriate therapy is recommended. Additionally, rare instances of intestinal angioedema have been reported with angiotensin-converting enzyme (ACE) inhibitors, including lisinopril.

Hypotension-related adverse effects have been noted in clinical trials, with incidences 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. Other clinical adverse experiences occurring in more than 1% of patients treated with lisinopril plus hydrochlorothiazide in controlled trials include dizziness (7.5%), headache (5.2%), cough (3.9%), fatigue (3.7%), and orthostatic effects (3.2%).

Adverse experiences reported have been consistent with those previously documented for lisinopril or hydrochlorothiazide. Rare cases of neutropenia, thrombocytopenia, and bone marrow depression have been reported, with a causal relationship to lisinopril not being excluded. Hemolytic anemia has also been reported, and while a causal relationship cannot be excluded, it remains uncertain.

Marketing experience has revealed rare instances of neutropenia and bone marrow depression, where a causal relationship to lisinopril cannot be excluded. Furthermore, ACE inhibitors have been infrequently 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 underlying this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or significant elevations in hepatic enzymes should discontinue the medication and receive appropriate medical follow-up.

Hydrochlorothiazide has been linked to an increased risk of non-melanoma skin cancer.

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

Patient Counseling

Healthcare providers should advise patients that if pregnancy is detected, lisinopril and hydrochlorothiazide tablets should be discontinued as soon as possible. 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 further doses until they have consulted with their prescribing physician.

Caution should be given to patients regarding the potential for lightheadedness, particularly during the initial days of therapy. If patients experience actual syncope, they should be instructed to discontinue the medication and consult their physician.

All patients must be made aware that excessive perspiration and dehydration can lead to a significant drop in blood pressure due to reduced fluid volume. Other factors that may cause volume depletion, such as vomiting or diarrhea, can also result in decreased blood pressure; therefore, patients should be encouraged to consult with their physician in such cases.

Patients should be informed not to use salt substitutes that contain potassium without prior consultation with their physician. Additionally, they should be advised to promptly report any signs of infection, such as a sore throat or fever, as these may indicate neutropenia.

Female patients of childbearing age should be counseled on the risks associated with 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 report any pregnancies to their physicians as soon as possible.

For patients taking hydrochlorothiazide, it is important to instruct them 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, particularly in patients experiencing excessive vomiting or receiving parenteral fluids. Clinicians should ensure that serum and urine electrolyte levels are assessed at appropriate intervals.

Patients should be counseled on several important safety considerations. They must report any signs of angioedema, such as swelling of the face, extremities, or difficulty in breathing, and refrain from taking further medication until consulting their physician. Patients are also advised to be vigilant for lightheadedness, especially during the initial days of therapy, and to discontinue the drug if syncope occurs. Additionally, they should be aware that excessive perspiration, dehydration, or other causes of volume depletion may lead to significant drops in blood pressure. Patients should avoid potassium-containing salt substitutes without prior consultation and report any signs of infection, as these may indicate neutropenia. Female patients of childbearing age should discuss the implications of treatment during pregnancy and 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 due to the risk of non-melanoma skin cancer.

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)