Hydrochlorothiazide/Lisinopril

Description

Lisinopril, a synthetic peptide derivative, is chemically described as (S)-1-N2-(1-carboxy-3-phenylpropyl)-L-lysyl-L-proline dihydrate. Its empirical formula is C21H31N3O5•2H2O, and it has a molecular weight of 441.53. Lisinopril appears as a white, crystalline powder that is soluble in water, sparingly soluble in methanol, and practically insoluble in ethanol.

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

Lisinopril and hydrochlorothiazide tablets USP are available for oral use in three tablet combinations: 10 mg/12.5 mg, 20 mg/12.5 mg, and 20 mg/25 mg. Inactive ingredients include dibasic calcium phosphate, magnesium stearate, mannitol, pregelatinized starch, and starch (corn). The 10 mg/12.5 mg tablet also contains FD&C Blue No. 2 Aluminum Lake, the 20 mg/12.5 mg tablet contains yellow iron oxide, and the 20 mg/25 mg tablet contains red iron oxide.

Uses and Indications

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

Control of hypertension should be integrated into a comprehensive cardiovascular risk management strategy, which encompasses lipid control, diabetes management, antithrombotic therapy, smoking cessation, physical activity, and dietary sodium restriction. It is important to note that many patients may require a combination of antihypertensive medications to achieve their blood pressure targets.

Clinical evidence from randomized controlled trials has demonstrated that various antihypertensive agents can significantly reduce cardiovascular morbidity and mortality. The most substantial and consistent benefit observed is a reduction in the risk of stroke, although decreases in myocardial infarction and overall cardiovascular mortality have also been frequently reported.

Elevated systolic or diastolic blood pressure is associated with increased cardiovascular risk, with the absolute risk increase per mmHg being more pronounced 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 different populations, but the absolute benefit is more pronounced in individuals at higher risk, such as those with diabetes or hyperlipidemia.

It is also noted that certain antihypertensive medications may exhibit diminished efficacy as monotherapy in black patients. Additionally, many antihypertensive drugs possess 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 are as follows: lisinopril can be administered at doses of 10 mg to 80 mg, while hydrochlorothiazide should be given 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 combination therapy with Lisinopril/HCTZ may be appropriate. The initial combination doses can be Lisinopril/HCTZ 10/12.5 mg or Lisinopril/HCTZ 20/12.5 mg, depending on the patient's current monotherapy dosage.

Further adjustments to the doses of either or both components 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.

After the addition of hydrochlorothiazide, it may be feasible to reduce the dose of lisinopril. If discontinuation of the diuretic is not possible, an initial dose of 5 mg of lisinopril should be administered under medical supervision, with monitoring for at least two hours until blood pressure stabilizes for an additional hour.

Contraindications

Lisinopril and hydrochlorothiazide is contraindicated in patients with hypersensitivity to this product. It 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.

The hydrochlorothiazide component contraindicates use in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. Additionally, this product should not be used in combination with a neprilysin inhibitor, such as sacubitril; administration of Lisinopril and Hydrochlorothiazide tablets USP should be avoided within 36 hours of switching to or from sacubitril/valsartan.

Co-administration of aliskiren with lisinopril and hydrochlorothiazide is contraindicated in patients with diabetes.

Warnings and Precautions

Patients receiving ACE inhibitors, including lisinopril and hydrochlorothiazide, may experience a range of adverse reactions, some of which can be serious.

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, it is imperative to discontinue lisinopril and hydrochlorothiazide immediately and provide appropriate therapy and monitoring until complete resolution of symptoms is achieved. Fatalities have been reported in rare cases due to angioedema associated with laryngeal or tongue edema. Additionally, intestinal angioedema has been documented, with symptoms resolving upon cessation of the ACE inhibitor.

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

Hypotension and Related Effects Excessive hypotension may arise in patients who are salt or volume-depleted, such as those receiving aggressive diuretic therapy or patients on dialysis. Initiation of therapy in patients with severe congestive heart failure should be conducted under close medical supervision.

Hematological Monitoring Leukopenia, neutropenia, and agranulocytosis have been associated with ACE inhibitor therapy. Therefore, periodic monitoring of white blood cell counts is recommended for patients with collagen vascular disease and renal disease.

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

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. Additionally, patients with renal disease may experience azotemia and should be monitored closely.

Laboratory Tests It is advisable to consider periodic monitoring of white blood cell counts in patients with collagen vascular disease and renal disease.

Emergency Medical Help In cases where there is involvement of the tongue, glottis, or larynx that 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 implemented.

Discontinuation and Medical Consultation Patients receiving ACE inhibitors who develop jaundice or marked elevations in hepatic enzymes should discontinue the medication and consult their healthcare provider for further evaluation and management.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. The most common adverse reactions, occurring in at least 1% of participants, 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). Additional common reactions are 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).

Serious adverse reactions have also been reported. Angioedema, involving swelling of the face, extremities, lips, tongue, glottis, and/or larynx, has been documented, with rare cases of intestinal angioedema noted in post-marketing experience. Hypotension-related adverse effects were observed 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, persistent nonproductive cough has been associated with the use of ACE inhibitors, typically resolving upon discontinuation of therapy.

Other adverse reactions reported include chest pain, abdominal pain, syncope, chest discomfort, fever, trauma, and viral infections. Cardiovascular effects such as palpitations and orthostatic hypotension, as well as gastrointestinal issues like cramps, dry mouth, constipation, and heartburn, have also been noted. Musculoskeletal complaints include back pain, shoulder pain, knee pain, back strain, myalgia, and foot pain. Nervous system and psychiatric effects may manifest as decreased libido, vertigo, depression, and somnolence. Respiratory issues include common cold, nasal congestion, influenza, bronchitis, pharyngeal pain, dyspnea, pulmonary congestion, chronic sinusitis, allergic rhinitis, and pharyngeal discomfort. Skin reactions may involve flushing, pruritus, skin inflammation, diaphoresis, and cutaneous pseudolymphoma. Special senses may be affected, leading to blurred vision, tinnitus, and otalgia. Urogenital adverse reactions include urinary tract infections.

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

Drug Interactions

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

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 non-steroidal anti-inflammatory drugs (NSAIDs) with lisinopril can result in renal function deterioration, particularly in elderly or volume-depleted patients. Additionally, the antihypertensive effect of lisinopril may be diminished by NSAIDs.

• Dual RAS Blockade: The use of lisinopril in conjunction with other agents that block the renin-angiotensin system (RAS) can heighten the risks of hypotension, hyperkalemia, and alterations in renal function.

• Aliskiren: Lisinopril should not be used with aliskiren in diabetic patients, and caution is warranted in patients with renal impairment (GFR < 60 mL/min).

• Potassium Levels: Lisinopril may elevate serum potassium levels when administered with potassium-sparing diuretics or potassium supplements; therefore, monitoring of serum potassium levels is recommended.

• Lithium: The combination of lisinopril and lithium may lead to lithium toxicity; it is essential to monitor serum lithium levels when these medications are used together.

• ACE Inhibitors and mTOR Inhibitors: The concurrent use of ACE inhibitors, including lisinopril, with mTOR inhibitors may increase the risk of angioedema.

• Neprilysin Inhibitors: Patients taking neprilysin inhibitors alongside lisinopril may also face an elevated risk of angioedema.

Pharmacokinetic Interactions:

• Hydrochlorothiazide: The use of hydrochlorothiazide with alcohol, barbiturates, or narcotics may enhance the risk of orthostatic hypotension. Antidiabetic medications may require dosage adjustments when used concurrently with hydrochlorothiazide. Furthermore, other antihypertensive agents may exhibit additive effects when combined with hydrochlorothiazide.

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

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

• Lithium and Diuretics: The combination of lithium with diuretics is generally discouraged due to an increased risk of toxicity.

• NSAIDs and Thiazide Diuretics: Non-steroidal anti-inflammatory drugs may diminish the effectiveness of thiazide diuretics, including hydrochlorothiazide.

• Gold and ACE Inhibitors: Nitritoid reactions have been reported with the use of injectable gold in conjunction with ACE inhibitors, including both lisinopril and hydrochlorothiazide.

Healthcare providers should carefully evaluate these interactions and consider appropriate monitoring or dosage adjustments as necessary to ensure patient safety and therapeutic efficacy.

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

Pediatric patients, particularly 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 renal function. Lisinopril, which is known to cross the placenta, has been effectively removed from neonatal circulation through peritoneal dialysis, and while exchange transfusion may theoretically aid in this process, there is currently no clinical experience to support its use.

The safety and effectiveness of this medication in pediatric patients have not been established, indicating a need for caution when considering its use 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, 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 medications. Given that this drug is primarily excreted by the kidneys, there is an elevated risk of toxic reactions in patients with impaired renal function.

Therefore, careful consideration must be given to renal function when evaluating hypertensive elderly patients, as they are more prone to renal impairment. Regular assessment of renal function is essential to ensure safe and effective dosing in this population.

Pregnancy

When pregnancy is detected, lisinopril and hydrochlorothiazide should be discontinued as soon as possible due to the risk of fetal toxicity. Drugs that act directly on the renin-angiotensin system, including lisinopril and hydrochlorothiazide, can cause significant injury and death to the developing fetus, particularly when used during the second and third trimesters. The use of these medications during this period is associated with reduced fetal renal function, increased fetal and neonatal morbidity, and mortality.

Oligohydramnios, a potential consequence of such drug use, can lead to serious fetal complications, including lung hypoplasia and skeletal deformations. Neonatal adverse effects may include skull hypoplasia, anuria, hypotension, renal failure, and death. While most epidemiologic studies examining fetal abnormalities following antihypertensive use in the first trimester have not specifically distinguished between drugs affecting the renin-angiotensin system and other antihypertensive agents, the risks associated with these medications are well-documented.

It is crucial to manage maternal hypertension appropriately during pregnancy to optimize outcomes for both the mother and fetus. In cases where there is no suitable alternative to therapy with renin-angiotensin system-affecting drugs, healthcare providers should inform the mother of the potential risks to the fetus. Serial ultrasound examinations should be performed to monitor the intra-amniotic environment, and if oligohydramnios is detected, lisinopril and hydrochlorothiazide should be discontinued unless deemed lifesaving for the mother.

Fetal testing may be warranted based on the gestational age, and both patients and physicians should be aware that oligohydramnios may not manifest until after the fetus has sustained irreversible injury. Infants with a history of in utero exposure to lisinopril and hydrochlorothiazide should be closely monitored for hypotension, oliguria, and hyperkalemia.

Teratogenicity studies conducted in pregnant rats, mice, and rabbits have not demonstrated teratogenic effects associated with lisinopril. However, in rats, decreased maternal weight gain and fetal weight were observed at doses as low as 3/10 mg/kg/day. It is important to note that when used during the second and third trimesters, ACE inhibitors can cause severe injury and even death to the developing 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 with lisinopril, are known to appear in human milk. Due to the potential for serious adverse reactions in breastfed infants from ACE inhibitors and hydrochlorothiazide, healthcare professionals should consider the risks and benefits when advising lactating mothers. A decision should be made regarding the discontinuation of nursing and/or the discontinuation of lisinopril and hydrochlorothiazide, taking into account the importance of the medication to the mother.

Renal Impairment

Patients with renal impairment require careful consideration regarding dosing adjustments and monitoring. Thiazide-containing combination products are not recommended for patients with severe renal dysfunction, as thiazides may precipitate azotemia and lead to cumulative effects in those with impaired renal function.

Periodic monitoring of white blood cell counts is advisable for patients with collagen vascular disease and renal disease. Additionally, excessive hypotension has been observed in patients with severe congestive heart failure, which may occur with or without associated renal insufficiency. This condition can lead to oliguria, progressive azotemia, and, in rare cases, acute renal failure or death.

Patients receiving ACE inhibitors, including lisinopril, may experience a range of adverse reactions, particularly those with renal impairment. A history of angioedema unrelated to ACE-inhibitor therapy may increase the risk of angioedema in these patients. In cases of severe renal dysfunction, dialysis should be halted immediately if anaphylactoid reactions occur, and aggressive therapy for such reactions must be initiated.

Close monitoring is essential during the first two weeks of treatment and whenever the dose of lisinopril and/or diuretic is increased. Syncope has been reported in patients receiving lisinopril, and the incidence may be reduced through proper titration of the individual components. Regular renal function tests and monitoring for hypotension are recommended for patients with renal impairment.

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, which may result in 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 compromised liver function or those with progressive liver disease. Minor alterations in fluid and electrolyte balance in these patients may precipitate hepatic coma, necessitating careful monitoring and management.

Overdosage

In the event of an overdosage of lisinopril and hydrochlorothiazide, specific treatment information is limited; therefore, management should be primarily symptomatic and supportive.

Lisinopril Overdosage

The most likely clinical manifestation of lisinopril overdosage is hypotension. In such cases, the recommended intervention is the intravenous infusion of normal saline solution to restore blood pressure. Animal studies indicate that 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 this dosage. It is important to note that lisinopril can be effectively removed from the body through hemodialysis, which may be considered in severe cases.

Hydrochlorothiazide Overdosage

For hydrochlorothiazide, a single oral dose of 10 g/kg administered to mice and rats was not lethal. However, common adverse effects associated with overdosage include electrolyte depletion and dehydration due to excessive diuresis. Clinicians should be vigilant for these signs and manage them accordingly. Additionally, if digitalis has been co-administered, hypokalemia resulting from hydrochlorothiazide may exacerbate the risk of cardiac arrhythmias, necessitating careful monitoring and appropriate corrective measures.

In summary, the management of overdosage for both lisinopril and hydrochlorothiazide should focus on supportive care, monitoring for hypotension, electrolyte imbalances, and potential complications related to co-administered medications.

Nonclinical Toxicology

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 fetal and neonatal morbidity and mortality. Oligohydramnios resulting from this use can contribute to fetal lung hypoplasia and skeletal deformations. Potential adverse neonatal effects include skull hypoplasia, anuria, hypotension, renal failure, and death. It is recommended to discontinue lisinopril and hydrochlorothiazide as soon as pregnancy is detected, particularly due to the adverse outcomes typically linked to their use during the second and third trimesters. Most epidemiologic studies investigating fetal abnormalities following antihypertensive exposure in the first trimester have not differentiated between drugs affecting the renin-angiotensin system and other antihypertensive agents.

In nonclinical studies, no teratogenic effects of lisinopril were observed in pregnant rats, mice, and rabbits, with doses administered being up to 625 times (in mice), 188 times (in rats), and 0.6 times (in rabbits) the maximum recommended human dose on a mg/kg basis. Teratogenicity studies conducted in mice and rats with doses of lisinopril up to 90 mg/kg/day (56 times the maximum recommended human dose) in combination with hydrochlorothiazide at 10 mg/kg/day (2.5 times the maximum recommended human dose) did not show maternal or fetotoxic effects in mice. However, in rats, decreased maternal weight gain and fetal weight were observed at doses as low as 3/10 mg/kg/day, which were associated with a delay in fetal ossification. These effects were not present in saline-supplemented animals receiving the combination of 90/10 mg/kg/day.

Non-teratogenic effects may include fetal or neonatal jaundice, thrombocytopenia, and potentially other adverse reactions observed in adults.

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, 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.

There was no evidence of tumorigenicity when lisinopril was administered for 105 weeks to male and female rats 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, respectively). Similarly, no evidence of carcinogenicity was found when lisinopril was administered for 92 weeks to male and female mice 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 using various strains of Salmonella typhimurium and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations. In vivo assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene did not indicate genotoxicity.

Studies in rats indicate that lisinopril poorly crosses the blood-brain barrier, and multiple doses do not result in tissue accumulation. However, the milk of lactating rats contains radioactivity following administration of 14C-lisinopril. Whole body autoradiography revealed radioactivity in the placenta of pregnant rats after administration of the labeled drug, but none was detected in the fetuses.

Postmarketing Experience

Postmarketing experience has identified an association between hydrochlorothiazide and an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma (SCC). Data derived from a study conducted within the Sentinel System indicate that this increased risk is notably observed in white patients who are administered large cumulative doses of the medication. Specifically, the overall population exhibits an approximate increase of 1 additional case of SCC per 16,000 patients per year. In contrast, white patients receiving a cumulative dose of ≥50,000 mg demonstrate a heightened risk, with an estimated 1 additional case of SCC occurring for every 6,700 patients per year.

Patient Counseling

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

Patients should be cautioned to report any instances of lightheadedness, particularly during the initial days of therapy. In the event of actual syncope, patients should be advised to discontinue the medication and seek guidance from their prescribing physician.

It is important to inform all patients that excessive perspiration and dehydration can lead to a significant drop in blood pressure due to reduced fluid volume. They should also be made aware that other factors contributing to volume depletion, such as vomiting or diarrhea, may similarly result in decreased blood pressure. Patients are encouraged to consult with their physician if they experience these conditions.

Patients should be instructed not to use salt substitutes that contain potassium without prior consultation with their physician.

Patients must be informed to report any signs of infection, such as a sore throat or fever, promptly, as these may indicate leukopenia or neutropenia.

Female patients of childbearing age should be made aware of the potential consequences of exposure to lisinopril and hydrochlorothiazide 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.

Patients taking hydrochlorothiazide should be instructed to protect their skin from sun exposure and to undergo regular skin cancer screenings.

Storage and Handling

The product is supplied in accordance with the National Drug Code (NDC) specifications. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), adhering to the guidelines set forth by the United States Pharmacopeia (USP) for Controlled Room Temperature.

It is essential to protect the product from excessive light and humidity to maintain its integrity and efficacy. Proper storage conditions are crucial for ensuring the quality of the product throughout its shelf life.

Additional Clinical Information

Periodic determination of serum electrolytes is recommended to detect potential electrolyte imbalances in patients, particularly those undergoing treatment with thiazides. Clinicians should assess renal function in hypertensive patients and monitor serum and urine electrolytes, especially in cases of excessive vomiting or parenteral fluid administration. Thiazides may increase urinary magnesium excretion, potentially leading to hypomagnesemia, and can decrease urinary calcium excretion, which may cause slight elevations in serum calcium levels. Notably, marked hypercalcemia could indicate hidden hyperparathyroidism, necessitating the discontinuation of thiazides prior to parathyroid function tests.

Patient counseling should emphasize the importance of reporting any signs of angioedema, such as facial or extremity swelling and difficulty breathing, immediately to a physician. Patients should be advised to monitor for lightheadedness, particularly during the initial days of therapy, and to discontinue the medication if syncope occurs until consulting their physician. Caution is warranted regarding excessive perspiration and dehydration, which can lead to significant drops in blood pressure. Patients should avoid potassium-containing salt substitutes without prior consultation and report any signs of infection that may indicate leukopenia or neutropenia. Female patients of childbearing age should be informed about the risks associated with lisinopril and hydrochlorothiazide during pregnancy and should report any pregnancies to their healthcare provider. Additionally, patients taking hydrochlorothiazide should be advised 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)