Quinapril hydrochloride/Hydrochlorothiazide

Description

Quinapril and hydrochlorothiazide tablets, USP are fixed-combination tablets that incorporate 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 a molecular formula of C25H30N2O5·HCl. It appears as a white to off-white amorphous powder that 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 a molecular formula of C7H8ClN3O4S2. This component is a white to off-white crystalline powder, slightly soluble in water and freely soluble in sodium hydroxide solution.

These tablets are formulated for oral administration and are available in three strengths: 10 mg of quinapril (equivalent to 10.832 mg of quinapril hydrochloride) combined with 12.5 mg of hydrochlorothiazide (quinapril and hydrochlorothiazide 10/12.5), 20 mg of quinapril (equivalent to 21.664 mg of quinapril hydrochloride) with 12.5 mg of hydrochlorothiazide (quinapril and hydrochlorothiazide 20/12.5), and 20 mg of quinapril (equivalent to 21.664 mg of quinapril hydrochloride) with 25 mg of hydrochlorothiazide (quinapril and hydrochlorothiazide 20/25). The strength of the quinapril hydrochloride component is expressed in terms of quinapril. Inactive ingredients include lactose monohydrate, magnesium carbonate, crospovidone, povidone, magnesium stearate, hypromellose, hydroxypropyl cellulose, polyethylene glycol 400, titanium dioxide, iron oxide red, and iron oxide yellow.

Uses and Indications

Quinapril and hydrochlorothiazide tablets are indicated for the treatment of hypertension to lower blood pressure. Effective management of hypertension is essential for reducing the risk of both fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.

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

The most significant cardiovascular outcome benefit observed with this treatment is a reduction in the risk of stroke, alongside reductions in myocardial infarction and cardiovascular mortality. Elevated systolic or diastolic blood pressure is associated with increased cardiovascular risk, with a greater absolute risk increase per mmHg at higher blood pressures. Even modest reductions in severe hypertension can yield substantial benefits.

The relative risk reduction from blood pressure lowering is consistent across various populations with differing absolute risks, with greater absolute benefits seen in patients at higher risk, such as those with diabetes or hyperlipidemia. It is also noted that some antihypertensive medications may exhibit smaller blood pressure effects as monotherapy in black patients, and many have additional approved indications and effects, including those related to angina, heart failure, or diabetic kidney disease.

This fixed combination of quinapril and hydrochlorothiazide is not indicated for the initial therapy of hypertension.

Dosage and Administration

Quinapril is indicated for administration in once-daily doses ranging from 10 mg to 80 mg. Hydrochlorothiazide is effective at doses between 12.5 mg and 50 mg. In clinical trials involving the combination therapy of quinapril and hydrochlorothiazide, quinapril doses were utilized in the range of 2.5 mg to 40 mg, while hydrochlorothiazide doses ranged from 6.25 mg to 25 mg.

For patients whose blood pressure is not adequately controlled with quinapril monotherapy, the combination of quinapril and hydrochlorothiazide may be initiated using tablets containing either 10 mg of quinapril with 12.5 mg of hydrochlorothiazide or 20 mg of quinapril with 12.5 mg of hydrochlorothiazide. Adjustments to the dosage of either component may be made based on the clinical response of the patient. It is recommended that the dose of hydrochlorothiazide should not be increased until a period of 2 to 3 weeks has elapsed to allow for assessment of the patient's response.

Patients who are adequately managed on a regimen of 20 mg of quinapril and 25 mg of hydrochlorothiazide may be transitioned to the combination tablets containing 20 mg of quinapril and 25 mg of hydrochlorothiazide. It is important to note that therapy regimens with quinapril and hydrochlorothiazide tablets do not require adjustments based on renal function, provided that the patient's creatinine clearance is greater than 30 mL/min/1.73 m².

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 treatment with an ACE inhibitor, should not use this medication.

The combination of quinapril and hydrochlorothiazide tablets with a neprilysin inhibitor, such as sacubitril, is contraindicated. Administration of this product should not occur within 36 hours of switching to or from sacubitril/valsartan.

Additionally, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

Co-administration with aliskiren is contraindicated in patients with diabetes.

Warnings and Precautions

Patients receiving ACE inhibitors, including quinapril, may experience a range of adverse reactions, some of which can be serious. Anaphylactoid reactions and angioedema are notable concerns. Angioedema can manifest as swelling of the face, extremities, lips, tongue, glottis, and larynx, with laryngeal edema posing a risk of fatality. In the event of laryngeal stridor or angioedema affecting the face, tongue, or glottis, it is imperative to discontinue treatment with quinapril and hydrochlorothiazide immediately.

Patients undergoing concomitant therapy with mTOR inhibitors or neprilysin inhibitors may have an elevated risk of developing angioedema. Additionally, those with a history of angioedema unrelated to ACE inhibitor therapy should be monitored closely, as they may also be at increased risk. Life-threatening anaphylactoid reactions have been reported in patients receiving ACE inhibitors during desensitization procedures.

Hepatic failure is another serious risk associated with ACE inhibitors, which may present as cholestatic jaundice and can progress to fulminant hepatic necrosis, potentially resulting in death. If jaundice or significant elevations in hepatic enzymes are observed, the ACE inhibitor should be discontinued, and appropriate medical follow-up should be initiated.

Quinapril and hydrochlorothiazide can lead to symptomatic hypotension, particularly in patients at risk for excessive drops in blood pressure. Close monitoring is recommended for these individuals. Furthermore, caution is advised when prescribing to patients with severe renal impairment, and renal function should be monitored during the initial weeks of therapy.

Serum electrolyte levels should be assessed periodically, as both hyperkalemia and hypokalemia may occur. Hydrochlorothiazide can also affect glucose tolerance and elevate serum cholesterol and triglyceride levels. A persistent nonproductive cough has been reported with ACE inhibitors, which typically resolves upon discontinuation of the medication.

During surgical procedures or anesthesia, quinapril may inhibit the formation of angiotensin II, potentially leading to hypotension that can be managed through volume expansion. Prior to conducting tests of parathyroid function, it is advisable to interrupt therapy with quinapril and hydrochlorothiazide for several days.

In cases where there is involvement of the tongue, glottis, or larynx that may lead to airway obstruction, emergency medical assistance should be sought immediately. Subcutaneous epinephrine solution (1:1000, 0.3 to 0.5 mL) should be administered promptly in such situations. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, treatment with quinapril and hydrochlorothiazide must be discontinued without delay, and the healthcare provider should be contacted.

Side Effects

Common adverse reactions observed in clinical trials (≥1% incidence) included headache (6.7%), dizziness (4.8%), coughing (3.2%), and fatigue (2.9%). Other frequently reported reactions were myalgia (2.4%), viral infection (1.9%), rhinitis (2%), and nausea and/or vomiting (1.8%). Additional common reactions included 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%), vertigo (1%), and chest pain (1%).

Clinical adverse experiences occurring in 0.5% to <1% of participants included asthenia and malaise as body-wide reactions. Cardiovascular events such as palpitations, tachycardia, and hypotension were noted, with hypotension reported in 1.2% of patients during clinical trials. Serious cardiovascular events included heart failure, hyperkalemia, myocardial infarction, cerebrovascular accident, hypertensive crisis, angina pectoris, orthostatic hypotension, and cardiac rhythm disturbances. Gastrointestinal issues included dry mouth or throat, gastrointestinal hemorrhage, pancreatitis, and abnormal liver function tests. Nervous system reactions included nervousness, vertigo, and paresthesia. Respiratory events such as sinusitis and dyspnea were also reported. Integumentary reactions included pruritus, increased sweating, erythema multiforme, exfoliative dermatitis, photosensitivity reactions, alopecia, and pemphigus. Urogenital system reactions included acute renal failure, impotence, agranulocytosis, and thrombocytopenia.

Serious adverse reactions included angioedema, reported in 0.1% of patients receiving quinapril, and rare occurrences of hypotension. Hepatic failure has been rarely associated with cholestatic jaundice progressing to fulminant hepatic necrosis. Neutropenia and agranulocytosis were also reported as rare occurrences, particularly in patients with renal impairment or collagen vascular disease.

Postmarketing experience has revealed additional adverse reactions. An increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma, has been associated with hydrochlorothiazide. Other body-wide reactions included shock, accidental injury, neoplasm, cellulitis, ascites, generalized edema, and anaphylactoid reactions. Cardiovascular events such as bradycardia, cor pulmonale, vasculitis, and deep vein thrombosis were also noted. Digestive system issues included gastrointestinal carcinoma, cholestatic jaundice, hepatitis, esophagitis, vomiting, and diarrhea. Eye disorders such as acute myopia and acute angle closure glaucoma were reported. Hemic system reactions included anemia, while metabolic and nutritional disorders included weight loss. Musculoskeletal system reactions included myopathy, myositis, and arthritis. Neurological events included paralysis, hemiplegia, speech disorders, abnormal gait, meningism, and amnesia. Respiratory system reactions included pneumonia, asthma, respiratory infiltration, and lung disorders. Skin and appendage reactions included urticaria, macropapular rash, and petechiae. Special senses reactions included abnormal vision, and urogenital system reactions included kidney function abnormalities, albuminuria, pyuria, hematuria, and nephrosis.

Drug Interactions

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

The combination of ACE inhibitors, such as quinapril, with lithium has been associated with increased serum lithium levels and symptoms of lithium toxicity. The risk of lithium toxicity is further heightened when a thiazide diuretic, like hydrochlorothiazide, is used concurrently, as it reduces renal clearance of lithium. Therefore, caution is warranted when coadministering quinapril, hydrochlorothiazide, and lithium, with frequent monitoring of serum lithium levels recommended.

Dual blockade of the renin-angiotensin system (RAS) using angiotensin receptor blockers, ACE inhibitors, or aliskiren may increase the risks of hypotension, hyperkalemia, and renal function changes, including acute renal failure, compared to monotherapy. Most patients do not experience additional benefits from the combination of two RAS inhibitors. Consequently, the combined use of RAS inhibitors should generally be avoided, and patients receiving quinapril and hydrochlorothiazide alongside other RAS-affecting agents should have their blood pressure, renal function, and electrolytes closely monitored.

Aliskiren should not be coadministered with quinapril and hydrochlorothiazide 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 considered 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 coadministration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors like quinapril may lead to renal function deterioration, potentially resulting in acute renal failure. These effects are typically reversible, and renal function should be monitored periodically in patients receiving quinapril and NSAID therapy. Additionally, the antihypertensive effect of ACE inhibitors may be diminished by NSAIDs.

Patients on concomitant mTOR inhibitors (e.g., temsirolimus) or neprilysin inhibitors may have 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, is not significantly altered by the coadministration of quinapril.

Thiazide-induced electrolyte disturbances, such as hypokalemia and hypomagnesemia, increase the risk of digoxin toxicity, which may lead to fatal arrhythmic events.

Concomitant use of alcohol, barbiturates, or narcotics may potentiate orthostatic hypotension.

For patients taking antidiabetic drugs (oral hypoglycemic agents and insulin), dosage adjustments may be necessary.

The absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins, such as cholestyramine and colestipol. Single doses of cholestyramine or colestipol can bind hydrochlorothiazide, reducing its gastrointestinal absorption by up to 85% and 43%, respectively.

Corticosteroids and ACTH may lead to intensified electrolyte depletion, particularly hypokalemia.

The response to pressor amines (e.g., norepinephrine) may be decreased, although this is not sufficient to preclude their therapeutic use.

Concurrent administration of non-steroidal anti-inflammatory drugs may reduce the diuretic, natriuretic, and antihypertensive effects of thiazide diuretics.

Packaging & NDC

The table below lists all NDC Code configurations of Quinapril Hydrochloride/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 quinapril and hydrochlorothiazide, may require careful monitoring. In cases of oliguria or hypotension, it is essential to support blood pressure and renal perfusion. Interventions such as exchange transfusions or dialysis may be necessary to address hypotension and/or substitute for impaired renal function. However, the removal of quinapril from the neonatal circulation is not significantly accelerated by these methods, as quinapril crosses the placenta.

The safety and effectiveness of quinapril and hydrochlorothiazide in children have not been established, necessitating caution when considering their use in this population.

Geriatric Use

Clinical studies of quinapril hydrochloride/hydrochlorothiazide did not include a sufficient number of subjects aged 65 and over to determine whether these elderly patients respond differently from younger subjects. However, other reported clinical experience has not identified significant differences in responses between geriatric patients and their younger counterparts.

In general, dose selection for elderly patients should be approached with caution. It is recommended 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 advised to ensure safety and efficacy.

Pregnancy

Quinapril and hydrochlorothiazide have not been evaluated for carcinogenicity, mutagenicity, or fertility in animal studies. However, quinapril hydrochloride was not found to be carcinogenic in mice or rats at doses up to 75 or 100 mg/kg/day over a 104-week period. Notably, female rats receiving the highest dose exhibited an increased incidence of mesenteric lymph node hemangiomas and skin/subcutaneous lipomas. In mutagenicity assessments, neither quinapril nor its active metabolite, quinaprilat, demonstrated mutagenic potential in the Ames bacterial assay, both with and without metabolic activation.

Regarding reproductive toxicity, studies indicate that quinapril does not adversely affect fertility or reproduction in rats at doses up to 100 mg/kg/day. Similarly, hydrochlorothiazide has shown no genotoxic effects in in vitro assays and did not negatively impact fertility in mice and rats of both sexes when administered doses of up to 100 mg/kg/day and 4 mg/kg/day, respectively, prior to mating and throughout gestation.

Given the lack of comprehensive studies on the effects of quinapril and hydrochlorothiazide during pregnancy, healthcare professionals should exercise caution when prescribing these medications to pregnant patients. The potential risks to fetal outcomes remain unclear, and the decision to use these agents should involve a careful assessment of the benefits versus risks in the context of individual patient circumstances.

Lactation

Quinapril and hydrochlorothiazide are secreted in human milk; therefore, caution should be exercised when administering this combination to lactating mothers. Due to the potential for serious adverse reactions in breastfed infants from hydrochlorothiazide and the unknown effects of quinapril, a decision should be made regarding whether to discontinue nursing or to discontinue quinapril and hydrochlorothiazide. This decision should consider the importance of the medication to the mother.

Renal Impairment

Quinapril and hydrochlorothiazide 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, inhibition of the renin-angiotensin-aldosterone system 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 treatment with angiotensin-converting enzyme (ACE) inhibitors, including quinapril, in hypertensive patients with unilateral renal artery stenosis is associated with increases in blood urea nitrogen and serum creatinine. These increases are typically reversible upon discontinuation of the ACE inhibitor, concomitant diuretic, or both.

During the initial weeks of therapy with quinapril and hydrochlorothiazide, renal function should be closely monitored, particularly in patients with pre-existing renal impairment, as some patients may experience increases in blood urea nitrogen and serum creatinine, usually minor and transient, especially when quinapril is administered with a diuretic. A dosage reduction of quinapril and hydrochlorothiazide may be necessary in these cases. Additionally, evaluation of hypertensive patients should include an assessment of renal function.

Hepatic Impairment

Patients with hepatic impairment should use quinapril and hydrochlorothiazide with caution due to the potential for minor alterations in fluid and electrolyte balance, which 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 the event that a patient receiving an ACE inhibitor develops jaundice or exhibits marked elevations in hepatic enzymes, the ACE inhibitor should be discontinued immediately, and appropriate medical follow-up should be initiated to ensure patient safety and manage any potential complications.

Overdosage

In cases of overdosage with quinapril and hydrochlorothiazide, specific treatment information is limited. Management should focus on symptomatic and supportive care. It is recommended that therapy with quinapril and hydrochlorothiazide be discontinued, and the patient should be closely monitored. Key concerns include dehydration, electrolyte imbalances, and hypotension, which should be addressed according to established medical protocols.

The oral median lethal dose for the combination of quinapril and hydrochlorothiazide has been observed in animal studies, ranging from 1063/664 mg/kg to 4640/2896 mg/kg in mice and rats. Notably, doses of quinapril between 1440 to 4280 mg/kg have resulted in significant lethality in these animal models. In single-dose studies involving hydrochlorothiazide, most rats survived doses up to 2.75 g/kg.

Human data regarding overdoses of ACE inhibitors, including quinapril, are limited. The most likely manifestation of quinapril overdosage in humans is hypotension. In contrast, overdose with hydrochlorothiazide typically presents with signs and symptoms related to dehydration and electrolyte depletion, such as hypokalemia, hypochloremia, and hyponatremia. It is important to note that if digitalis has been administered concurrently, hypokalemia may exacerbate the risk of cardiac arrhythmias.

Laboratory assessments of serum levels of quinapril and its metabolites are not commonly available, and such determinations do not have 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.

While angiotensin II could theoretically act as a specific antagonist or antidote in the event 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, it is reasonable to manage quinapril overdose through the infusion of normal saline solution to restore fluid balance.

Nonclinical Toxicology

Carcinogenicity, mutagenicity, and fertility studies have not been conducted in animals with quinapril and hydrochlorothiazide. Quinapril hydrochloride was not carcinogenic in mice or rats when administered at doses 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 the maximum human daily dose on a mg/m² basis. However, female rats receiving the highest dose exhibited an increased incidence of mesenteric lymph node hemangiomas and skin/subcutaneous lipomas.

Neither quinapril nor quinaprilat demonstrated mutagenic potential in the Ames bacterial assay, both with and without metabolic activation. Quinapril was also negative in several genetic toxicology studies, including in vitro mammalian cell point mutation, sister chromatid exchange in cultured mammalian cells, micronucleus test with mice, in vitro chromosome aberration with V79 cultured lung cells, and in vivo cytogenetic study with rat bone marrow. Additionally, there were no adverse effects on fertility or reproduction observed in rats at doses up to 100 mg/kg/day.

Under the auspices of the National Toxicology Program, hydrochlorothiazide was administered in feed to rats and mice for 2 years at doses up to 600 mg/kg/day in mice and up to 100 mg/kg/day in rats. These studies revealed no evidence of carcinogenic potential for hydrochlorothiazide in rats or female mice; however, there was equivocal evidence of hepatocarcinogenicity in male mice. Hydrochlorothiazide was not 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.

Positive results were observed in the in vitro CHO sister chromatid exchange test and in the mouse lymphoma cell assays at concentrations of hydrochlorothiazide ranging from 43 to 1300 mcg/mL. Additionally, positive results were obtained in the Aspergillus nidulans nondisjunction assay. Hydrochlorothiazide did not adversely affect the fertility of mice and rats of either sex in studies where these species were exposed to doses of up to 100 and 4 mg/kg/day, respectively, prior to mating and throughout gestation.

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). Data from a study conducted in the Sentinel System indicate that the increased risk is predominantly observed in white patients receiving large cumulative doses. The overall population shows an approximate risk of 1 additional case of SCC per 16,000 patients per year, while white patients with a cumulative dose of ≥50,000 mg exhibit an increased risk of 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 a causal relationship.

Patient Counseling

Healthcare providers should advise patients to discontinue quinapril and hydrochlorothiazide as soon as pregnancy is detected. It is important for patients to immediately report any signs or symptoms of angioedema, such as swelling of the face, eyes, lips, or tongue, or difficulty in breathing. Patients should temporarily discontinue the medication until they have consulted with their prescribing physician.

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

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

Patients should be informed 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.

Those planning to undergo major surgery or general or spinal anesthesia should inform their physicians that they are taking an ACE inhibitor. Additionally, patients receiving quinapril and hydrochlorothiazide 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. Furthermore, 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 various package configurations, with specific NDC numbers available upon request. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F) in accordance with USP Controlled Room Temperature guidelines.

Additionally, it is essential to protect the product from light to maintain its integrity and efficacy. Proper handling and storage conditions must be adhered to in order to ensure optimal product quality.

Additional Clinical Information

The hydrochlorothiazide component of quinapril and hydrochlorothiazide may lead to a decrease in serum protein-bound iodine (PBI) levels, although this effect does not indicate any thyroid disturbance. Clinicians should consider interrupting therapy with quinapril and hydrochlorothiazide for several days prior to conducting tests to assess parathyroid function in patients.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Quinapril Hydrochloride/Hydrochlorothiazide as submitted by Aurobindo Pharma Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)