Quinapril hydrochloride/Hydrochlorothiazide

Description

Quinapril and Hydrochlorothiazide Tablets, USP are a fixed-combination formulation that incorporates quinapril hydrochloride, an angiotensin-converting enzyme (ACE) inhibitor, and hydrochlorothiazide, a thiazide diuretic. Quinapril hydrochloride is chemically defined as [3S-[2R*(R*), 3R*]]-2-[2-[1-(ethoxycarbonyl)-3-phenylpropylamino]-1-oxopropyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid, monohydrochloride, with an empirical formula of C25H30N2O5·HCl. It appears as a white to off-white amorphous powder, occasionally exhibiting a pink cast, and is freely soluble in aqueous solvents.

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

Quinapril and Hydrochlorothiazide Tablets, USP are formulated for oral administration and are available in three strengths: 10 mg of quinapril (equivalent to 10.83 mg of quinapril hydrochloride) with 12.5 mg of hydrochlorothiazide, 20 mg of quinapril (equivalent to 21.66 mg of quinapril hydrochloride) with 12.5 mg of hydrochlorothiazide, and 20 mg of quinapril (equivalent to 21.66 mg of quinapril hydrochloride) with 25 mg of hydrochlorothiazide. The tablets contain inactive ingredients including magnesium hydroxide, microcrystalline cellulose, crospovidone, magnesium stearate, polyvinyl alcohol, titanium dioxide, talc, soy lecithin, FD&C Yellow No. 6, and xanthan gum.

Uses and Indications

Quinapril 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 nonfatal 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 targets.

Clinical evidence from randomized controlled trials has demonstrated that various antihypertensive agents can significantly reduce cardiovascular morbidity and mortality. The most substantial cardiovascular outcome 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 experiencing greater absolute benefits, regardless of their hypertension status.

Dosage and Administration

Quinapril is administered orally as a once-daily dose, with effective dosing ranging from 10 mg to 80 mg. For hydrochlorothiazide, the effective dosing range is 12.5 mg to 50 mg. In clinical trials involving the combination therapy of quinapril and hydrochlorothiazide, quinapril was utilized at doses between 2.5 mg and 40 mg, while hydrochlorothiazide was used at doses from 6.25 mg to 25 mg.

For patients whose blood pressure remains inadequately controlled with quinapril monotherapy, the combination of quinapril and hydrochlorothiazide tablets at doses of 10/12.5 mg or 20/12.5 mg may be considered. Adjustments to the dosage of either component may be made based on clinical response, but it is recommended that the hydrochlorothiazide dose not be increased until a period of 2 to 3 weeks has elapsed.

Patients who are adequately managed on a regimen of 20 mg of quinapril and 25 mg of hydrochlorothiazide may transition to the combination tablets of quinapril and hydrochlorothiazide at a dose of 20/25 mg.

Contraindications

Quinapril and hydrochlorothiazide tablets are contraindicated in the following situations:

• Patients with hypersensitivity to quinapril or hydrochlorothiazide, as well as those with a history of angioedema related to previous ACE inhibitor treatment, due to the risk of severe allergic reactions.

• Co-administration with neprilysin inhibitors, such as sacubitril, is contraindicated. Quinapril and hydrochlorothiazide tablets should not be administered within 36 hours of switching to or from sacubitril/valsartan to avoid potential adverse effects.

• Patients with anuria or hypersensitivity to other sulfonamide-derived drugs should not use this product, as it may exacerbate their condition.

• Co-administration with aliskiren is contraindicated in patients with diabetes, due to the increased risk of renal impairment and other adverse effects.

Warnings and Precautions

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

Anaphylactoid and Angioedema Reactions Angioedema affecting the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with ACE inhibitors. In the event of laryngeal stridor or angioedema involving the face, tongue, or glottis, it is imperative to discontinue treatment with quinapril and hydrochlorothiazide tablets immediately. Patients should receive treatment in accordance with established medical protocols, which may include the prompt administration of emergency therapy such as subcutaneous epinephrine solution 1:1000 (0.3 to 0.5 mL) if airway obstruction is likely.

History of Angioedema Patients with a prior history of angioedema unrelated to ACE inhibitor therapy may be at an increased risk for angioedema while receiving an ACE inhibitor.

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

Management of Hypotension In cases of excessive hypotension, patients should be placed in a supine position, and if necessary, treated with an intravenous infusion of normal saline. Should symptomatic hypotension occur, a reduction in dosage or discontinuation of quinapril and hydrochlorothiazide tablets may be warranted.

Renal Function Assessment Renal function should be closely monitored during the initial weeks of therapy in patients treated with quinapril and hydrochlorothiazide tablets to ensure safety and efficacy.

Neutropenia and Agranulocytosis Monitoring Periodic monitoring of white blood cell counts is recommended for patients with collagen vascular disease and/or renal disease due to the risk of neutropenia or agranulocytosis.

Fetal Toxicity Considerations In the event of a confirmed pregnancy, it is crucial to discontinue quinapril and hydrochlorothiazide tablets as soon as possible, as medications that act directly on the renin-angiotensin system can cause injury or death to the developing fetus.

Emergency Medical Assistance Patients should seek emergency medical help if they experience laryngeal stridor or angioedema affecting the face, tongue, or glottis.

Discontinuation and Consultation Patients should stop taking quinapril and hydrochlorothiazide tablets and contact their healthcare provider if they develop jaundice, marked elevations in hepatic enzymes, or experience excessive hypotension.

Side Effects

Patients receiving treatment may experience a range of adverse reactions, which can be categorized by frequency and seriousness.

Common adverse reactions occurring in 1% or more of participants in controlled trials include headache (6.7%), dizziness (4.8%), coughing (3.2%), and fatigue (2.9%). Other notable reactions include myalgia (2.4%), viral infection (1.9%), rhinitis (2.0%), and nausea and/or vomiting (1.8%). Additional common reactions are abdominal pain (1.7%), back pain (1.5%), diarrhea (1.4%), upper respiratory infection (1.3%), insomnia (1.2%), somnolence (1.2%), bronchitis (1.2%), dyspepsia (1.2%), asthenia (1.1%), pharyngitis (1.1%), vasodilatation (1.0%), vertigo (1.0%), and chest pain (1.0%).

Serious adverse reactions reported include angioedema, which occurred in 0.1% of patients receiving quinapril, and hypotension, reported in 1.2% of patients during clinical trials. Neutropenia and agranulocytosis have been rarely associated with ACE inhibitors, including quinapril.

Additional adverse reactions noted in clinical practice encompass a variety of systems. Body-wide reactions may include asthenia, malaise, shock, accidental injury, neoplasm, cellulitis, ascites, generalized edema, hernia, and anaphylactoid reactions. Cardiovascular events may involve palpitations, tachycardia, heart failure, hyperkalemia, myocardial infarction, cerebrovascular accident, hypertensive crisis, angina pectoris, orthostatic hypotension, and cardiac rhythm disturbances. Gastrointestinal reactions can include dry mouth or throat, gastrointestinal hemorrhage, pancreatitis, and abnormal liver function tests. Neurological and psychiatric effects may manifest as nervousness, vertigo, and paresthesia. Respiratory issues may include sinusitis and dyspnea. Integumentary reactions can involve pruritus, increased sweating, erythema multiforme, exfoliative dermatitis, photosensitivity reactions, alopecia, and pemphigus. Urogenital system reactions may include acute renal failure and impotence. Other serious reactions reported include agranulocytosis, thrombocytopenia, and arthralgia.

Postmarketing experiences have identified additional risks, such as an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma, associated with hydrochlorothiazide. Rare cases of hepatic failure have been reported, beginning with cholestatic jaundice and potentially progressing to fulminant hepatic necrosis. Acute angle-closure glaucoma has also been noted with hydrochlorothiazide, which can lead to permanent visual field loss if not treated promptly.

Laboratory test findings indicate that hyperkalemia occurred in approximately 2% of patients, while hydrochlorothiazide may cause hypokalemia and hyponatremia. Furthermore, hydrochlorothiazide may alter glucose tolerance and elevate serum cholesterol and triglycerides.

Warnings include the potential for fetal toxicity; treatment should be discontinued if pregnancy is detected, as it can cause injury and death to the developing fetus. Anaphylactoid reactions may occur, particularly in patients with a history of angioedema or those receiving concomitant mTOR inhibitors.

Drug Interactions

Coadministration of quinapril and hydrochlorothiazide tablets with other medications that elevate serum potassium levels may lead to hyperkalemia. It is advised to monitor serum potassium levels in these patients.

When quinapril and hydrochlorothiazide tablets are used in conjunction with lithium, there is an increased risk of elevated serum lithium levels and potential lithium toxicity. This risk is further heightened when a thiazide diuretic is also administered. Therefore, caution is warranted, and frequent monitoring of serum lithium levels is recommended.

The dual blockade of the renin-angiotensin system (RAS) through the use of angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with heightened risks of hypotension, hyperkalemia, and alterations in renal function, including acute renal failure, compared to monotherapy. It is advisable to avoid the combined use of RAS inhibitors and to closely monitor blood pressure, renal function, and electrolyte levels in patients receiving quinapril and hydrochlorothiazide tablets alongside other RAS-affecting agents.

Aliskiren should not be co-administered with quinapril and hydrochlorothiazide tablets in patients with diabetes or those with renal impairment (GFR < 60 mL/min/1.73 m²).

The simultaneous administration of tetracycline with quinapril may reduce the absorption of tetracycline by approximately 28% to 37%, likely due to the high magnesium content in quinapril tablets. This interaction should be taken into account when prescribing quinapril alongside tetracycline or other magnesium-interacting drugs.

Rare instances of nitritoid reactions, characterized by facial flushing, nausea, vomiting, and hypotension, have been reported in patients receiving injectable gold (sodium aurothiomalate) in conjunction with ACE inhibitors.

In elderly patients, those who are volume-depleted (including individuals on diuretic therapy), or those with compromised renal function, the co-administration of nonsteroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, with ACE inhibitors such as quinapril may lead to renal function deterioration, including the risk of acute renal failure. Periodic monitoring of renal function is recommended for patients receiving quinapril alongside NSAIDs. Additionally, the antihypertensive effect of ACE inhibitors may be diminished by NSAIDs.

Patients undergoing treatment with mTOR inhibitors (e.g., temsirolimus) or neprilysin inhibitors may experience an increased risk of angioedema.

No pharmacokinetic interactions were observed when single doses of quinapril and hydrochlorothiazide were administered together. However, multiple doses of propranolol or cimetidine do not affect the pharmacokinetics of single doses of quinapril.

The anticoagulant effect of a single dose of warfarin, as measured by prothrombin time, remains largely unchanged with the coadministration of quinapril.

Thiazide-induced electrolyte disturbances, such as hypokalemia and hypomagnesemia, can increase the risk of digoxin toxicity, potentially leading to fatal arrhythmic events.

Alcohol, barbiturates, or narcotics may enhance the risk of orthostatic hypotension. Antidiabetic medications, including oral hypoglycemic agents and insulin, may necessitate dosage adjustments.

The absorption of hydrochlorothiazide is significantly impaired in the presence of anionic exchange resins, such as cholestyramine and colestipol, with reductions in absorption of up to 85% and 43%, respectively.

Corticosteroids and ACTH may exacerbate electrolyte depletion, particularly hypokalemia. There may also be a possible decreased response to pressor amines (e.g., norepinephrine), although this is not sufficient to preclude their therapeutic use. Conversely, there may be an increased responsiveness to non-depolarizing skeletal muscle relaxants (e.g., tubocurarine).

The diuretic, natriuretic, and antihypertensive effects of thiazide diuretics may be diminished by the concurrent administration of nonsteroidal anti-inflammatory agents.

Packaging & NDC

The table below lists all NDC Code configurations of Quinapril and Hydrochlorothiazide, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of quinapril and hydrochlorothiazide tablets in pediatric patients have not been established. Therefore, caution is advised when considering the use of this medication in children. Further studies are necessary to determine appropriate dosing and outcomes in this population.

Geriatric Use

Clinical studies of quinapril HCl/hydrochlorothiazide did not include a sufficient number 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. Careful monitoring of these patients is recommended to ensure safety and efficacy.

Pregnancy

Pregnant patients and women of childbearing potential should be informed about the potential consequences of exposure to quinapril and hydrochlorothiazide tablets during pregnancy. It is essential for healthcare providers to discuss treatment options with women who are planning to become pregnant, ensuring that the benefits and risks are carefully considered.

Patients are advised to report any pregnancies to their physicians as soon as possible to facilitate appropriate management and monitoring.

Lactation

There are no specific statements regarding nursing mothers or lactation considerations in the provided text. Therefore, the effects of this medication on breastfed infants and its excretion in breast milk remain undetermined. Healthcare professionals should exercise caution when prescribing this medication to lactating mothers, considering the absence of data on its safety and efficacy during breastfeeding.

Renal Impairment

Quinapril and hydrochlorothiazide tablets should be used with caution in patients with severe renal disease, as thiazides may precipitate azotemia in these individuals, and the effects of repeated dosing may be cumulative. In patients with severe congestive heart failure, where renal function may depend on the renin-angiotensin-aldosterone system, inhibition by quinapril may lead to anticipated changes in renal function, including oliguria, progressive azotemia, and, in rare cases, acute renal failure or death.

Clinical studies have shown that hypertensive patients with unilateral renal artery stenosis treated with ACE inhibitors, including quinapril, experienced increases in blood urea nitrogen and serum creatinine, which were reversible upon discontinuation of the medication or concomitant diuretic. Therefore, renal function should be closely monitored during the first few weeks of therapy in such patients.

Additionally, some hypertensive patients treated with quinapril, even without apparent preexisting renal vascular diseases, have developed minor and transient increases in blood urea nitrogen and serum creatinine, particularly when quinapril is administered with a diuretic. This occurrence is more likely in patients with pre-existing renal impairment, and dosage reduction of quinapril and hydrochlorothiazide tablets may be necessary.

Evaluation of hypertensive patients should include an assessment of renal function, and periodic monitoring of white blood cell counts in patients with collagen vascular disease and/or renal disease is advisable.

Hepatic Impairment

Quinapril and hydrochlorothiazide tablets should be used with caution in patients with impaired hepatic function or progressive liver disease, as minor alterations in fluid and electrolyte balance may precipitate hepatic coma. The metabolism of quinapril to its active form, quinaprilat, is primarily dependent on hepatic esterases; therefore, patients with compromised liver function may experience significantly elevated plasma levels of quinapril.

Currently, no pharmacokinetic studies have been conducted specifically in hypertensive patients with impaired liver function, which limits the understanding of the drug's behavior in this population. It is essential for healthcare providers to monitor patients closely for any signs of liver dysfunction. In cases where patients receiving ACE inhibitors develop jaundice or marked elevations in hepatic enzymes, it is recommended that the ACE inhibitor be discontinued, and appropriate medical follow-up should be initiated.

Overdosage

In the event of an overdosage with quinapril and hydrochlorothiazide tablets, specific treatment information is limited. Management should focus on symptomatic and supportive care. It is recommended that therapy with quinapril and hydrochlorothiazide tablets be discontinued immediately, and the patient should be closely monitored.

Potential Symptoms

The most likely manifestation of quinapril overdosage in humans is hypotension. In cases of hydrochlorothiazide overdose, common symptoms include dehydration and electrolyte depletion, which may present as hypokalemia, hypochloremia, and hyponatremia. If the patient has also received digitalis, hypokalemia may exacerbate the risk of cardiac arrhythmias.

Management Procedures

Treatment of dehydration, electrolyte imbalances, and hypotension should follow established medical protocols. The oral median lethal dose of quinapril/hydrochlorothiazide in animal studies ranges from 1063/664 to 4640/2896 mg/kg in mice and rats, with significant lethality observed at doses of 1440 to 4280 mg/kg of quinapril. In single-dose studies, most rats survived doses of hydrochlorothiazide up to 2.75 g/kg.

Laboratory assessments of serum levels of quinapril and its metabolites are not commonly available and do not play a defined role in the management of quinapril overdose. Furthermore, there is no evidence to support the use of physiological maneuvers, such as altering urine pH, to enhance the elimination of quinapril and its metabolites.

Both hemodialysis and peritoneal dialysis have been shown to have minimal impact on the elimination of quinapril and quinaprilat. Although angiotensin II could theoretically act as a specific antagonist-antidote in cases of quinapril overdose, it is largely unavailable outside of specialized research settings. Given that the hypotensive effects of quinapril result from vasodilation and effective hypovolemia, the infusion of normal saline solution is a reasonable approach to managing quinapril overdose.

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. This can result in oligohydramnios, which is linked to fetal lung hypoplasia and skeletal deformations. Potential adverse effects in neonates may include skull hypoplasia, anuria, hypotension, renal failure, and death.

In studies involving pregnant rats and rabbits, no teratogenic effects of quinapril were observed, even at doses up to 180 times the maximum recommended human dose in rats and one time in rabbits on a mg/kg basis. Similarly, quinapril and hydrochlorothiazide tablets did not demonstrate teratogenic effects in these animal studies, with doses reaching up to 188/94 times the maximum recommended human dose in rats and 0.6/0.3 times in rabbits.

Intrauterine exposure to thiazide diuretics has been linked to fetal or neonatal jaundice, thrombocytopenia, and potentially other adverse reactions that may also occur in adults.

Carcinogenicity, mutagenicity, and fertility studies have not been conducted in animals with quinapril and hydrochlorothiazide tablets. However, quinapril hydrochloride was not found to be carcinogenic in mice or rats when administered doses of up to 75 or 100 mg/kg/day for 104 weeks, which corresponds to 50 or 60 times the maximum human daily dose on a mg/kg basis and 3.8 or 10 times on a mg/m² basis. An increased incidence of mesenteric lymph node hemangiomas and skin/subcutaneous lipomas was noted in female rats at the highest dose level.

Neither quinapril nor quinaprilat exhibited mutagenic properties in the Ames bacterial assay, both with and without metabolic activation. Quinapril also tested negative in various genetic toxicology studies, including in vitro mammalian cell point mutation, sister chromatid exchange, micronucleus tests in mice, in vitro chromosome aberration tests, and in vivo cytogenetic studies with rat bone marrow.

Fertility and reproduction studies in rats indicated no adverse effects at doses up to 100 mg/kg/day, which is 60 and 10 times the maximum daily human dose based on mg/kg and mg/m², respectively. Hydrochlorothiazide was not found to be genotoxic in in vitro assays using various strains of Salmonella typhimurium, the Chinese hamster ovary test for chromosomal aberrations, or in vivo assays involving mouse germinal cell chromosomes and Chinese hamster bone marrow chromosomes. However, positive results were observed in the in vitro CHO sister chromatid exchange test and in mouse lymphoma cell assays at hydrochlorothiazide concentrations ranging from 43 to 1300 μg/mL.

Hydrochlorothiazide did not adversely affect fertility in mice and rats of either sex when exposed to doses of up to 100 and 4 mg/kg/day, respectively, prior to mating and throughout gestation.

Some placental passage of quinapril was noted in studies with pregnant rats, while research indicates that quinapril and its metabolites do not cross the blood-brain barrier. Hydrochlorothiazide, on the other hand, crosses the placenta freely but does not penetrate the blood-brain barrier.

Postmarketing Experience

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

Hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma (SCC), especially in white patients receiving large cumulative doses. In a study conducted within the Sentinel System, the overall risk for SCC was approximately 1 additional case per 16,000 patients per year. For white patients taking a cumulative dose of ≥50,000 mg, the risk increase was approximately 1 additional SCC case for every 6,700 patients per year.

Additional adverse events reported include:

Body as a Whole: Shock, accidental injury, neoplasm, cellulitis, ascites, generalized edema, hernia, and anaphylactoid reaction.

Cardiovascular System: Bradycardia, cor pulmonale, vasculitis, and deep vein thrombosis.

Digestive System: Gastrointestinal carcinoma, cholestatic jaundice, hepatitis, esophagitis, vomiting, and diarrhea.

Eye Disorders: Acute myopia and acute angle closure glaucoma.

Hemic System: Anemia.

Metabolic and Nutritional Disorders: Weight loss.

Musculoskeletal System: Myopathy, myositis, and arthritis.

Nervous System: Paralysis, hemiplegia, speech disorder, abnormal gait, meningism, and amnesia.

Respiratory System: Pneumonia, asthma, respiratory infiltration, and lung disorder.

Skin and Appendages: Urticaria, macropapular rash, and petechiae.

Special Senses: Abnormal vision.

Urogenital System: Abnormal kidney function, albuminuria, pyuria, hematuria, and nephrosis.

These events reflect the range of experiences reported in the postmarketing setting and do not imply causality.

Patient Counseling

Patients receiving quinapril and hydrochlorothiazide tablets should be advised to immediately report any signs or symptoms of angioedema, such as swelling of the face, eyes, lips, or tongue, or difficulty in breathing. They should temporarily discontinue the medication until they have consulted with their prescribing physician.

Female patients of childbearing age must be informed about the potential consequences of exposure to quinapril and hydrochlorothiazide tablets during pregnancy. Healthcare providers should discuss treatment options with women who are planning to become pregnant and encourage them to report any pregnancies to their physicians as soon as possible.

Patients should be made aware that lightheadedness may occur, particularly during the initial days of therapy, and they should report this to their prescribing physician. If syncope occurs, patients are advised to discontinue quinapril and hydrochlorothiazide tablets until they have consulted with their physician.

It is important to inform patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to a significant drop in blood pressure due to reduced fluid volume, which may result in lightheadedness and possible syncope.

Patients planning to undergo major surgery or general or spinal anesthesia should be instructed to inform their physicians that they are taking an ACE inhibitor.

Patients receiving quinapril and hydrochlorothiazide tablets should be cautioned against using potassium supplements or salt substitutes containing potassium without prior consultation with their prescribing physician.

Patients should promptly report any signs of infection, such as a sore throat or fever, as these may indicate neutropenia.

Additionally, patients taking hydrochlorothiazide should be advised to protect their skin from sun exposure and to undergo regular skin cancer screenings.

Storage and Handling

The product is supplied in tight containers as defined by the United States Pharmacopeia (USP). It should be stored at a temperature range of 20–25° C (68–77° F), in accordance with USP Controlled Room Temperature guidelines. Proper adherence to these storage conditions is essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

The hydrochlorothiazide component of quinapril and hydrochlorothiazide tablets may lead to decreased serum PBI levels without indicating thyroid disturbance. Clinicians should advise patients to interrupt therapy for a few days prior to conducting parathyroid function tests.

Patients receiving quinapril and hydrochlorothiazide tablets should be counseled to report any signs of angioedema, such as swelling of the face, eyes, lips, or tongue, or difficulty breathing, and to temporarily discontinue the medication until consulting their physician. Female patients of childbearing age should be informed about the risks of exposure during pregnancy and discuss treatment options if planning to conceive. Patients may experience lightheadedness, particularly during the initial days of therapy, and should report this to their physician; syncope should prompt immediate discontinuation of the medication until further consultation. Additionally, patients should be aware that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to significant drops in blood pressure. Those planning major surgery or anesthesia should inform their healthcare provider about their ACE inhibitor use. It is also important for patients not to use potassium supplements or salt substitutes containing potassium without prior consultation. Patients should promptly report any signs of infection, which may indicate neutropenia, and those taking hydrochlorothiazide should protect their skin from sun exposure and undergo regular skin cancer screenings.

Postmarketing data indicate that hydrochlorothiazide is associated with an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma (SCC), especially in white patients receiving high cumulative doses. The overall risk for SCC is approximately one additional case per 16,000 patients per year, increasing to one additional case for every 6,700 patients per year among white patients taking a cumulative dose of ≥50,000 mg.

FDA Insert (PDF)

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

View full prescribing information (PDF)