Lisinopril/Hydrochlorothiazide

Uses and Indications

Lisinopril and Hydrochlorothiazide Tablets is indicated for the treatment of hypertension, aimed at lowering blood pressure. Effective management of high blood pressure is essential for reducing the risk of both fatal and non-fatal cardiovascular events, particularly strokes and myocardial infarctions.

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

Clinical evidence from randomized controlled trials has demonstrated that numerous antihypertensive agents can significantly reduce cardiovascular morbidity and mortality. The most substantial and consistent cardiovascular outcome benefit observed is a reduction in the risk of stroke, with additional reductions in myocardial infarction and cardiovascular mortality frequently reported.

Elevated systolic or diastolic blood pressure is associated with 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 health benefits. The relative risk reduction associated with blood pressure lowering is consistent across various 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 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, clinical trials have demonstrated the efficacy of lisinopril doses from 10 mg to 80 mg alongside hydrochlorothiazide doses from 6.25 mg to 50 mg.

In cases where blood pressure remains inadequately controlled with either lisinopril or hydrochlorothiazide monotherapy, healthcare professionals may consider switching the patient to Lisinopril and Hydrochlorothiazide Tablets at dosages of 10/12.5 mg or 20/12.5 mg. Further adjustments to the dosage of either component may be made based on the clinical response, with the understanding that increases in hydrochlorothiazide should generally not occur until 2 to 3 weeks have passed.

It is important to note that dosages exceeding 80 mg of lisinopril and 50 mg of hydrochlorothiazide are not recommended. The combination therapy may be utilized as a substitute for the titrated individual components without necessitating adjustments to the usual regimens, provided that the patient's creatinine clearance remains above 30 mL/min/1.73 m² (serum creatinine approximately less than or equal to 3 mg/dL or 265 µmol/L).

Contraindications

Lisinopril and Hydrochlorothiazide Tablets are contraindicated in patients with hypersensitivity to any component of the formulation. The use of this product is also contraindicated in individuals with a history of angioedema associated with prior treatment using an angiotensin-converting enzyme 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, coadministration with neprilysin inhibitors, such as sacubitril, is contraindicated; Lisinopril and Hydrochlorothiazide Tablets should not be administered within 36 hours of switching to or from sacubitril/valsartan. Furthermore, the use of aliskiren in conjunction with Lisinopril and Hydrochlorothiazide Tablets is contraindicated in patients with diabetes.

Warnings and Precautions

Patients receiving Lisinopril and Hydrochlorothiazide Tablets should be aware of several critical warnings and precautions associated with their use.

Anaphylactoid and Related Reactions Patients may experience a range of adverse reactions, including serious anaphylactoid reactions. Angioedema, which can affect the face, extremities, lips, tongue, glottis, and/or larynx, has been reported rarely and may occur at any time during treatment. In such instances, Lisinopril and Hydrochlorothiazide Tablets should be discontinued immediately. Patients with a history of angioedema unrelated to ACE-inhibitor therapy may be at an increased risk for angioedema while receiving an ACE inhibitor. Additionally, coadministration of an ACE inhibitor with an mTOR inhibitor or a neprilysin inhibitor may further elevate this risk. Intestinal angioedema has also been reported, presenting with abdominal pain, which resolved upon discontinuation of the ACE inhibitor.

Hypotension and Related Effects Excessive hypotension may occur, 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, if necessary, receive an intravenous infusion of normal saline.

Neutropenia/Agranulocytosis Rare cases of neutropenia and bone marrow depression have been documented. It is advisable to consider periodic monitoring of white blood cell counts in patients with collagen vascular disease and renal disease.

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

General Precautions Lisinopril should be administered with caution in patients with aortic stenosis or hypertrophic cardiomyopathy due to potential obstruction in the outflow tract of the left ventricle. Changes in renal function may occur in susceptible individuals; therefore, renal function should be monitored during the initial weeks of therapy. Patients with risk factors for hyperkalemia, such as renal insufficiency or concomitant use of potassium-sparing diuretics, should have their serum potassium levels monitored. A persistent nonproductive cough has been reported with ACE inhibitors, and caution is advised during major surgery or anesthesia, as Lisinopril may inhibit angiotensin II formation, potentially leading to hypotension.

Laboratory Tests Evaluation of renal function is essential in the assessment of hypertensive patients. Periodic determination of serum electrolytes is recommended to detect possible electrolyte imbalances at appropriate intervals.

Emergency Medical Help In cases where there is involvement of 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/or measures to ensure a patent airway should be undertaken.

Healthcare professionals are advised to remain vigilant regarding these warnings and precautions to ensure patient safety during treatment with Lisinopril and Hydrochlorothiazide Tablets.

Side Effects

Common adverse reactions observed in clinical trials include dizziness (7.5%), headache (5.2%), cough (3.9%), fatigue (3.7%), and orthostatic effects (3.2%). Other frequently reported reactions are 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%).

Adverse reactions occurring in 0.3 to 1.0 percent of patients include a variety of symptoms across different systems. Body-related reactions include chest pain, abdominal pain, syncope, chest discomfort, fever, trauma, and viral infections. Cardiovascular effects consist of palpitations and orthostatic hypotension. Digestive issues reported are gastrointestinal cramps, dry mouth, constipation, and heartburn. Musculoskeletal complaints include back pain, shoulder pain, knee pain, back strain, myalgia, and foot pain. Nervous and psychiatric reactions encompass decreased libido, vertigo, depression, and somnolence. Respiratory symptoms include common cold, nasal congestion, influenza, bronchitis, pharyngeal pain, dyspnea, pulmonary congestion, chronic sinusitis, allergic rhinitis, and pharyngeal discomfort. Skin-related reactions involve flushing, pruritus, skin inflammation, and diaphoresis. Special senses may be affected by blurred vision, tinnitus, and otalgia, while urogenital issues include urinary tract infections.

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

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

Additional adverse reactions include rare cases of neutropenia, thrombocytopenia, and bone marrow depression, as well as hemolytic anemia, for which a causal relationship to lisinopril cannot be excluded. 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.

Skin reactions reported include urticaria, alopecia, herpes zoster, photosensitivity, skin lesions, skin infections, pemphigus, erythema, and psoriasis. Other severe skin reactions, such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and cutaneous pseudolymphoma, have been reported rarely, although a causal relationship has not been established. A symptom complex has also been reported, which may include a positive ANA, elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia, fever, vasculitis, leukocytosis, eosinophilia, photosensitivity, rash, and other dermatological manifestations.

Drug Interactions

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

Pharmacodynamic Interactions:

• Diuretics: Patients on diuretic therapy may experience excessive hypotension upon initiation of lisinopril. To mitigate this risk, it is advisable to either discontinue the diuretic or increase salt intake prior to starting lisinopril.

• Non-steroidal Anti-inflammatory Agents (NSAIDs): Co-administration of NSAIDs, including selective COX-2 inhibitors, may lead to renal function deterioration, particularly in elderly patients, those who are volume-depleted, or individuals with pre-existing renal impairment. Additionally, the antihypertensive effect of lisinopril may be diminished. Close monitoring of renal function is recommended.

• Dual Blockade of the Renin-Angiotensin System (RAS): The combination of lisinopril with other RAS inhibitors, such as angiotensin receptor blockers or direct renin inhibitors (e.g., aliskiren), increases the risk of hypotension, syncope, hyperkalemia, and renal function changes, including acute renal failure.

• Agents Increasing Serum Potassium: Caution is advised when using lisinopril with potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes, as these combinations may lead to significant hyperkalemia. Regular monitoring of serum potassium levels is recommended.

• Lithium: The concomitant use of lisinopril and lithium has been associated with increased lithium toxicity. Frequent monitoring of serum lithium levels is essential.

• Gold: Rare nitritoid reactions, such as facial flushing, nausea, vomiting, and hypotension, have been reported when injectable gold is used with ACE inhibitors like lisinopril.

• mTOR Inhibitors and Neprilysin Inhibitors: Co-administration with these agents may increase the risk of angioedema.

Pharmacokinetic Interactions:

• Hydrochlorothiazide: When used with alcohol, barbiturates, or narcotics, there is a potential for enhanced orthostatic hypotension.

• Antidiabetic Drugs: Dosage adjustments may be necessary for antidiabetic medications when used concurrently with hydrochlorothiazide.

• Other Antihypertensive Drugs: There may be an additive effect or potentiation of antihypertensive effects when hydrochlorothiazide is combined with other antihypertensive agents.

• Cholestyramine and Colestipol Resins: These resins can significantly impair the absorption of hydrochlorothiazide, reducing its bioavailability by up to 85% and 43%, respectively.

• Corticosteroids and ACTH: The use of these agents may lead to intensified electrolyte depletion, particularly hypokalemia.

• Pressor Amines (e.g., Norepinephrine): There is a possibility of decreased response to pressor amines when used with hydrochlorothiazide.

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

• Lithium: Hydrochlorothiazide can reduce the renal clearance of lithium, increasing the risk of lithium toxicity.

• Non-steroidal Anti-inflammatory Drugs: The effectiveness of diuretics, including their diuretic, natriuretic, and antihypertensive effects, may be reduced when used with NSAIDs. Close monitoring for therapeutic efficacy is advised.

In summary, careful consideration of these interactions and appropriate monitoring can help optimize patient safety and therapeutic outcomes when using lisinopril and hydrochlorothiazide.

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/or to compensate for impaired renal function.

Lisinopril is known to cross the placenta, and peritoneal dialysis has been utilized to remove it from neonatal circulation, demonstrating some clinical benefit. Although theoretically, exchange transfusion could also facilitate the removal of Lisinopril, there is currently no clinical experience supporting this procedure in neonates.

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 about 80% in elderly hypertensive patients compared to their younger counterparts. Given that this medication is significantly 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 renal function when selecting doses for elderly patients. Regular assessment of renal function is essential in the evaluation of hypertensive patients, particularly in the geriatric population, to ensure safe and effective treatment.

Pregnancy

Lisinopril is contraindicated in pregnancy due to the potential risk to the fetus when used during this period. The use of lisinopril has been associated with adverse fetal outcomes, particularly during the second and third trimesters, which may include injury or death to the developing fetus.

Hydrochlorothiazide is also not recommended for use during pregnancy due to potential risks. Although animal studies have shown no adverse effects on reproductive performance in male and female rats treated with lisinopril at doses up to 300 mg/kg/day (33 times the maximum recommended human dose based on body surface area), the implications for human pregnancy remain concerning. Similarly, hydrochlorothiazide did not adversely affect fertility in mice and rats exposed to doses of up to 100 mg/kg and 4 mg/kg, respectively, prior to conception and throughout gestation.

Healthcare professionals should exercise caution and consider alternative therapies for pregnant patients or women of childbearing potential.

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 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 these agents may precipitate azotemia and exhibit cumulative effects in individuals with reduced kidney function. In patients with severe renal disease, careful monitoring is essential due to the risk of adverse effects.

Captopril, another angiotensin-converting enzyme (ACE) inhibitor, has been associated with agranulocytosis and bone marrow depression, particularly in patients with renal impairment and those with collagen vascular diseases. While clinical trial data for lisinopril are insufficient to definitively rule out similar risks, marketing experience has noted rare instances of neutropenia and bone marrow depression potentially linked to lisinopril. Therefore, periodic monitoring of white blood cell counts is advisable for patients with both collagen vascular disease and renal disease.

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

Additionally, patients receiving a combination of an ACE inhibitor and mTOR inhibitors (such as temsirolimus, sirolimus, or everolimus) or a neprilysin inhibitor may face an increased risk of angioedema. Excessive hypotension, while rarely observed in uncomplicated hypertensive patients, remains a potential risk in those who are salt- or volume-depleted, such as individuals undergoing vigorous diuretic therapy or those on dialysis.

Hepatic Impairment

Patients with hepatic impairment may experience an increased risk of adverse effects when treated with ACE inhibitors. Rarely, these medications have been associated with a syndrome that begins with cholestatic jaundice or hepatitis and can progress to fulminant hepatic necrosis, and in some cases, death. The underlying mechanism of this syndrome remains unclear.

In patients receiving ACE inhibitors, if jaundice or significant elevations in hepatic enzymes are observed, it is imperative to discontinue the ACE inhibitor immediately and ensure appropriate medical follow-up is provided.

Thiazide diuretics should be administered with caution in patients with impaired hepatic function or progressive liver disease. Minor alterations in fluid and electrolyte balance in these patients may precipitate hepatic coma, necessitating careful monitoring and potential dosage adjustments.

Overdosage

In cases of overdosage with Lisinopril and Hydrochlorothiazide Tablets, specific treatment 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, suggested measures include the induction of emesis and/or gastric lavage to reduce the absorption of the drug. Additionally, it is crucial to correct any dehydration, electrolyte imbalances, and hypotension using established medical procedures.

Potential Symptoms

The most likely manifestation of an overdose is hypotension. The standard treatment for hypotension in this context would involve the intravenous infusion of normal saline solution. Common signs and symptoms associated with overdosage may include those resulting from electrolyte depletion, such as hypokalemia, hypochloremia, and hyponatremia, as well as dehydration due to excessive diuresis.

It is important to note that if digitalis has been administered concurrently, hypokalemia may exacerbate the risk of cardiac arrhythmias.

Additional Considerations

Animal studies indicate that following a single oral dose of 20 g/kg, no lethality was observed 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. Lisinopril can be effectively removed from the system through hemodialysis, which may be considered in severe cases of overdose.

Healthcare professionals should remain vigilant and provide appropriate supportive care to manage the symptoms and complications associated with overdosage.

Nonclinical Toxicology

No teratogenic effects were observed in the studies conducted. In non-teratogenic assessments, lisinopril administered at doses up to 300 mg/kg/day did not adversely affect reproductive performance in male and female rats, which is 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. These doses correspond 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, both with and without metabolic activation. Additionally, no DNA single strand breaks were produced in an in vitro alkaline elution assay using rat hepatocytes, nor were there increases in chromosomal aberrations in either an in vitro test with Chinese hamster ovary cells or an in vivo study involving mouse bone marrow.

Long-term studies indicated no 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. Hydrochlorothiazide was also 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 not genotoxic in in vitro assays, including the Ames mutagenicity assay with various Salmonella typhimurium strains and the Chinese Hamster Ovary (CHO) test for chromosomal aberrations. Furthermore, it did not exhibit genotoxicity in in vivo assays involving mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, or the Drosophila sex-linked recessive lethal trait gene. Positive results were only noted in the in vitro CHO Sister Chromatid Exchange (clastogenicity) and Mouse Lymphoma Cell (mutagenicity) assays at specific concentrations, as well as in the Aspergillus nidulans non-disjunction assay at an unspecified concentration.

Postmarketing Experience

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

Syncope has been documented in 0.8% of patients receiving Lisinopril and Hydrochlorothiazide Tablets, while the incidence in patients treated with lisinopril alone is 0.1%. Proper titration of the individual components may reduce the overall incidence of syncope.

In patients with severe congestive heart failure, with or without renal insufficiency, excessive hypotension has been observed, which may be associated with oliguria, progressive azotemia, and, in rare cases, acute renal failure or death. Due to the potential for significant blood pressure reduction in these patients, therapy should be initiated under close medical supervision.

Rare cases of a syndrome characterized by cholestatic jaundice or hepatitis progressing to fulminant hepatic necrosis and, occasionally, death have been associated with ACE inhibitors, although the underlying mechanism remains unclear. Additionally, marketing experience has revealed rare instances of neutropenia and bone marrow depression, where a causal relationship to lisinopril cannot be excluded. It is advisable to consider periodic monitoring of white blood cell counts in patients with collagen vascular disease and renal disease.

Patients receiving coadministration of ACE inhibitors and mTOR inhibitors (e.g., temsirolimus, sirolimus, everolimus) may be at an increased risk for angioedema. Similarly, those taking concomitant neprilysin inhibitors may also face an elevated risk for this condition.

In clinical trials, hyperkalemia (serum potassium greater than 5.7 mEq/L) occurred in approximately 1.4% of hypertensive patients treated with lisinopril plus hydrochlorothiazide. Most instances were isolated values that resolved despite continued therapy, and hyperkalemia was not a reason for discontinuation of treatment.

Angioedema affecting the face, extremities, lips, tongue, glottis, and/or larynx has been reported rarely in patients treated with angiotensin-converting enzyme inhibitors, including lisinopril, and may occur at any time during treatment.

Patient Counseling

Patients should be advised to discontinue Lisinopril and Hydrochlorothiazide Tablets as soon as pregnancy is detected. It is important to inform them that medications acting directly on the renin-angiotensin system can cause injury and even death to a developing fetus.

Patients must be instructed to report immediately 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 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 seek guidance from their physician.

All patients should be made aware that excessive perspiration and dehydration can lead to a significant drop in blood pressure due to reduced fluid volume. They should also be informed that other factors, such as vomiting or diarrhea, may contribute to volume depletion and a subsequent fall in blood pressure, warranting consultation with their physician.

Patients should be advised against using salt substitutes that contain potassium without prior consultation with their physician. Additionally, they should be instructed to 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 they should be encouraged to report any pregnancies to their physicians as soon as possible.

For those taking hydrochlorothiazide, patients should be instructed to protect their skin from sun exposure and to undergo regular skin cancer screenings.

Storage and Handling

The product is supplied in a tight, light-resistant container, in accordance with USP/NF standards. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), as defined by USP Controlled Room Temperature. Care should be taken to protect the product from excessive light and humidity to ensure its integrity and efficacy.

Additional Clinical Information

Patients should be informed about several important safety considerations while using the medication. They must report any signs of angioedema, such as swelling of the face, extremities, or difficulty in breathing, to their physician immediately and refrain from taking further doses until they have consulted with their healthcare provider. Additionally, patients should be cautioned about the risk of symptomatic hypotension, particularly during the initial days of therapy, and should discontinue use if they experience syncope, seeking medical advice thereafter.

Patients are also advised regarding the potential for hyperkalemia, specifically to avoid potassium-containing salt substitutes without prior consultation with their physician. Signs of neutropenia, such as sore throat or fever, should prompt immediate reporting to a healthcare professional. Female patients of childbearing age should be made aware of the risks associated with the medication during pregnancy and should discuss treatment options if they are planning to conceive. Furthermore, those taking hydrochlorothiazide should be instructed to protect their skin from sun exposure and to participate in 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 Actavis Pharma, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)