Quinapril hydrochloride/Hydrochlorothiazide

Description

Quinapril and Hydrochlorothiazide Tablets is 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 crystalline 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 compound is also 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) combined 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 carnauba wax NF, magnesium hydroxide USP, microcrystalline cellulose NF, crospovidone NF, magnesium stearate NF, polyvinyl alcohol-part hydrolyzed USP, titanium dioxide USP, talc USP, lecithin (soya) NF, FD&C yellow #6/sunset yellow FCF aluminum lake, and xanthan gum.

Uses and Indications

Quinapril and Hydrochlorothiazide Tablets are indicated for the treatment of hypertension to lower blood pressure. Effective management of high blood pressure is essential as it reduces the risk of both fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.

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

Numerous antihypertensive agents have demonstrated efficacy in randomized controlled trials, showing a reduction in cardiovascular morbidity and mortality. The most significant cardiovascular outcome benefit observed is a reduction in the risk of stroke, although reductions in myocardial infarction and overall cardiovascular mortality have also been consistently reported.

Elevated systolic or diastolic blood pressure is associated with increased cardiovascular risk, and even modest reductions in severe hypertension can yield substantial health benefits. The relative risk reduction associated with blood pressure lowering is comparable across various populations with differing absolute risks, with patients at higher risk experiencing greater absolute benefits, regardless of their hypertension status.

Dosage and Administration

Quinapril is administered orally in once-daily doses ranging from 10 mg to 80 mg. Hydrochlorothiazide is also administered orally, with effective doses ranging from 12.5 mg to 50 mg. In clinical trials involving the combination therapy of quinapril and hydrochlorothiazide, quinapril was utilized in doses between 2.5 mg and 40 mg, while hydrochlorothiazide was used in 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 prescribed. 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 not be increased until a period of 2 to 3 weeks has elapsed to allow for adequate assessment of the patient's response.

Patients who are effectively managed on a regimen of 20 mg of quinapril and 25 mg of hydrochlorothiazide may transition to Quinapril and Hydrochlorothiazide Tablets at a combined dose of 20/25 mg. The combination tablet should be taken orally, ensuring adherence to the prescribed dosing schedule for optimal therapeutic outcomes.

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 product due to the risk of severe allergic reactions.

The combination of Quinapril and Hydrochlorothiazide Tablets with a neprilysin inhibitor, such as sacubitril, is contraindicated. Administration should not occur within 36 hours of switching to or from sacubitril/valsartan to avoid potential adverse effects.

This product is also contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs, as these conditions may lead to serious complications.

Additionally, 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 and Hydrochlorothiazide Tablets, 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 larynx, have 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.

In cases where angioedema involves the tongue, glottis, or larynx and poses a risk of airway obstruction, emergency therapy should be initiated without delay. This may include the administration of subcutaneous epinephrine solution (1:1000, 0.3 to 0.5 mL).

Intestinal Angioedema Intestinal angioedema has also been documented in patients on ACE inhibitors, with symptoms typically resolving upon discontinuation of the medication.

History of Angioedema Patients with a prior history of angioedema unrelated to ACE inhibitor therapy may have an increased risk of developing angioedema while on these medications.

Desensitization Treatment Life-threatening anaphylactoid reactions have been observed in patients undergoing desensitization treatment for Hymenoptera venom while receiving ACE inhibitors.

Hepatic and Renal Considerations Patients receiving ACE inhibitors who develop jaundice or significant elevations in hepatic enzymes should discontinue the medication and undergo appropriate medical evaluation. Additionally, renal function should be closely monitored during the initial weeks of therapy, particularly in patients with renal artery stenosis or severe renal disease.

Hypotension Management In cases of excessive hypotension, patients should be positioned supine, and intravenous infusion of normal saline may be necessary. A reduction in dosage or discontinuation of Quinapril and Hydrochlorothiazide Tablets may be warranted if symptomatic hypotension occurs.

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

Fetal Toxicity Quinapril and Hydrochlorothiazide Tablets should be discontinued as soon as pregnancy is confirmed. Medications that affect the renin-angiotensin system during the second and third trimesters can lead to serious injury or death of the developing fetus.

Impaired Hepatic Function Caution is advised when prescribing Quinapril and Hydrochlorothiazide Tablets to patients with impaired hepatic function or progressive liver disease.

Acute Angle-Closure Glaucoma Hydrochlorothiazide may induce an idiosyncratic reaction leading to acute angle-closure glaucoma. In such cases, the primary course of action is to discontinue hydrochlorothiazide as quickly as possible.

Healthcare professionals are encouraged to remain vigilant for these potential adverse effects and to monitor patients accordingly.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. The most common adverse reactions, occurring in 1% or more of participants in controlled trials, include headache (6.7%), dizziness (4.8%), coughing (3.2%), fatigue (2.9%), myalgia (2.4%), viral infection (1.9%), rhinitis (2.0%), nausea and/or vomiting (1.8%), 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%).

In addition to these common reactions, other adverse reactions have been reported, categorized by system. Notable reactions affecting the body as a whole include asthenia, malaise, shock, accidental injury, neoplasm, cellulitis, ascites, generalized edema, hernia, and anaphylactoid reactions. Cardiovascular events may include palpitations, tachycardia, heart failure, hyperkalemia, myocardial infarction, cerebrovascular accident, hypertensive crisis, angina pectoris, orthostatic hypotension, and cardiac rhythm disturbances. Gastrointestinal reactions can involve dry mouth or throat, gastrointestinal hemorrhage, pancreatitis, and abnormal liver function tests.

Nervous and psychiatric reactions may include nervousness, vertigo, and paresthesia. Respiratory adverse reactions include sinusitis and dyspnea. Integumentary reactions may manifest as pruritus, increased sweating, erythema multiforme, exfoliative dermatitis, photosensitivity reactions, alopecia, and pemphigus. Urogenital system reactions may include acute renal failure and impotence. Other significant reactions include agranulocytosis, thrombocytopenia, and arthralgia. Angioedema has been reported in 0.1% of patients receiving quinapril.

Postmarketing experience has revealed additional adverse reactions. There is an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma, associated with hydrochlorothiazide. Other body-wide reactions include weakness. Cardiovascular issues may involve orthostatic hypotension, which can be exacerbated by alcohol, barbiturates, or narcotics. Digestive system reactions reported include pancreatitis, jaundice (intrahepatic cholestatic), sialadenitis, vomiting, diarrhea, cramping, nausea, gastric irritation, constipation, and anorexia. Neurologic reactions may consist of vertigo, lightheadedness, transient blurred vision, headache, paresthesia, xanthopsia, weakness, and restlessness. Musculoskeletal reactions can include muscle spasms.

Hematologic reactions may involve aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, and hemolytic anemia. Renal adverse reactions include renal failure, renal dysfunction, and interstitial nephritis. Metabolic reactions may present as hyperglycemia, glycosuria, and hyperuricemia. Hypersensitivity reactions can include necrotizing angiitis, Stevens-Johnson syndrome, respiratory distress (including pneumonitis and pulmonary edema), purpura, urticaria, rash, and photosensitivity.

Drug Interactions

Coadministration of Quinapril and Hydrochlorothiazide Tablets with agents that increase serum potassium levels may lead to hyperkalemia. It is advisable to monitor serum potassium levels in patients receiving such combinations.

When used in conjunction with lithium, Quinapril and Hydrochlorothiazide Tablets may elevate serum lithium levels, increasing the risk of lithium toxicity. This risk is further heightened due to the renal clearance reduction of lithium caused by thiazide diuretics. Therefore, caution is warranted when coadministering these medications, 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 renal function alterations, including acute renal failure, compared to monotherapy. It is generally recommended to avoid the combined use of RAS inhibitors. Patients on Quinapril and Hydrochlorothiazide Tablets, along with other RAS-affecting agents, should have their blood pressure, renal function, and electrolytes closely monitored. Specifically, aliskiren should not be coadministered with Quinapril and Hydrochlorothiazide Tablets in patients with diabetes or 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 coprescribing these medications.

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

In elderly patients, those who are volume-depleted, or individuals with compromised renal function, the coadministration of non-steroidal anti-inflammatory drugs (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; however, renal function should be monitored periodically in patients receiving quinapril and NSAID therapy. Additionally, the antihypertensive effect of quinapril may be diminished by NSAIDs.

Patients taking mTOR inhibitors (e.g., temsirolimus) or neprilysin inhibitors may experience an increased risk of angioedema when these agents are used concurrently with Quinapril and Hydrochlorothiazide Tablets.

Other interactions include:

• Propranolol and cimetidine do not significantly affect the pharmacokinetics of quinapril.

• The anticoagulant effect of warfarin, as measured by prothrombin time, is not significantly altered by quinapril.

• Thiazide-induced electrolyte disturbances, such as hypokalemia and hypomagnesemia, may increase the risk of digoxin toxicity, potentially leading to fatal arrhythmias.

• No pharmacokinetic interaction was observed when single doses of quinapril and hydrochlorothiazide were administered together.

Concomitant use of thiazide diuretics with the following agents may lead to interactions:

• Alcohol, barbiturates, or narcotics may potentiate orthostatic hypotension.

• Antidiabetic drugs (oral hypoglycemic agents and insulin) may require dosage adjustments.

• Cholestyramine and colestipol resins can impair the absorption of hydrochlorothiazide, reducing its gastrointestinal absorption by up to 85% and 43%, respectively.

• Corticosteroids and ACTH may intensify electrolyte depletion, particularly hypokalemia.

• Pressor amines (e.g., norepinephrine) may exhibit a decreased response, although this does not preclude their therapeutic use.

• Nondepolarizing skeletal muscle relaxants (e.g., tubocurarine) may show increased responsiveness.

• The diuretic, natriuretic, and antihypertensive effects of thiazide diuretics may be reduced by concurrent administration of NSAIDs.

Packaging & NDC

The table below lists all NDC Code configurations of Quinapril Hcl 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 therapeutic 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 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

When pregnancy is detected, Quinapril and Hydrochlorothiazide Tablets should be discontinued as soon as possible due to the risk of fetal toxicity. Drugs that act directly on the renin-angiotensin system, including Quinapril, can cause injury and death to the developing fetus. The use of these medications during the second and third trimesters is particularly concerning, as they can reduce fetal renal function and increase the risk of fetal and neonatal morbidity and mortality.

Oligohydramnios, which may result from the use of these drugs, can lead to serious complications such as fetal lung hypoplasia and skeletal deformations. Potential adverse effects in neonates include skull hypoplasia, anuria, hypotension, renal failure, and death, with these outcomes typically associated with exposure during the later stages of pregnancy.

Most epidemiologic studies investigating fetal abnormalities following antihypertensive use in the first trimester have not specifically differentiated between drugs affecting the renin-angiotensin system and other antihypertensive agents. Therefore, appropriate management of maternal hypertension during pregnancy is crucial 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 are recommended to monitor the intra-amniotic environment, and if oligohydramnios is detected, Quinapril and Hydrochlorothiazide Tablets should be discontinued unless their use is deemed life-saving 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 Quinapril and Hydrochlorothiazide Tablets should be closely monitored for hypotension, oliguria, and hyperkalemia. Additionally, intrauterine exposure to thiazide diuretics has been associated with fetal or neonatal jaundice, thrombocytopenia, and potentially other adverse reactions observed in adults. Notably, no teratogenic effects of Quinapril were identified in studies involving pregnant rats and rabbits.

Lactation

Quinapril and hydrochlorothiazide are secreted in human milk; therefore, caution should be exercised when administering Quinapril and Hydrochlorothiazide Tablets 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 Tablets. This decision should consider the importance of the medication to the mother.

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 ACE inhibitor, concomitant diuretic, or both. 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 in the absence of apparent preexisting renal vascular diseases, have developed minor and transient increases in blood urea nitrogen and serum creatinine, particularly when quinapril is administered alongside 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. Regular assessment of renal function is recommended for hypertensive patients receiving this treatment.

Hepatic Impairment

Patients with hepatic impairment should use Quinapril and Hydrochlorothiazide Tablets with caution. Impaired hepatic function or progressive liver disease may lead to minor alterations in fluid and electrolyte balance, which could 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 markedly 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 receiving ACE inhibitors closely. If a patient develops jaundice or exhibits marked elevations in hepatic enzymes, the ACE inhibitor should be discontinued, and appropriate medical follow-up should be initiated.

Additionally, it is important to note that ACE inhibitors, including quinapril, have been rarely associated with a syndrome that begins with cholestatic jaundice and can progress to fulminant hepatic necrosis, which may result in death. The underlying mechanism of this syndrome remains unclear, necessitating careful consideration and monitoring in patients with hepatic impairment.

Overdosage

In the event of an overdosage of 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, and the patient should be closely monitored for any adverse effects.

Potential Symptoms of Overdosage

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 are no data to support the use of physiological maneuvers, such as altering urine pH, to enhance the elimination of quinapril and its metabolites. 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-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, it is advisable to manage quinapril overdose with the infusion of normal saline solution to restore fluid balance.

Nonclinical Toxicology

No teratogenic effects of quinapril were observed in studies involving pregnant rats and rabbits, with doses administered being up to 180 times the maximum recommended human dose in rats and equivalent to the maximum recommended human dose in rabbits. Similarly, no teratogenic effects were noted for Quinapril and Hydrochlorothiazide Tablets in studies with pregnant rats and rabbits, where the doses were up to 188/94 times in rats and 0.6/0.3 times in rabbits the maximum recommended human dose.

The use of drugs that influence the renin-angiotensin system during the second and third trimesters of pregnancy has been associated with reduced fetal renal function, leading to increased morbidity and mortality in both fetal and neonatal populations. This can result in oligohydramnios, which may be linked to fetal lung hypoplasia and skeletal deformities. Potential adverse effects in neonates include skull hypoplasia, anuria, hypotension, renal failure, and death. Additionally, intrauterine exposure to thiazide diuretics has been correlated with fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions observed in adults.

Carcinogenicity, mutagenicity, and fertility studies have not been conducted with Quinapril and Hydrochlorothiazide Tablets in animal models. 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 demonstrated 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, and in vitro chromosome aberration tests.

No adverse effects on fertility or reproduction were observed in rats 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 obtained in the in vitro CHO sister chromatid exchange test and in mouse lymphoma cell assays at concentrations of hydrochlorothiazide ranging from 43 to 1300 μg/mL. Hydrochlorothiazide did not adversely affect the fertility of 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 when administered to pregnant rats, while studies indicate 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). 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.

Patient Counseling

Patients receiving Quinapril and Hydrochlorothiazide Tablets should be advised to immediately report any signs or symptoms suggestive 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, they should discontinue the medication 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 controlled room temperature of 20–25 °C (68–77 °F) to ensure optimal stability and efficacy.

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 on several important safety considerations. They must be informed about the risk of angioedema, particularly after the first dose, and should report any signs such as swelling of the face, eyes, lips, or tongue, or difficulty breathing. Female patients of childbearing age should be made aware of the potential consequences of exposure during pregnancy and should report any pregnancies to their physician promptly. Patients should also be cautioned about the possibility of symptomatic hypotension, especially during the initial days of therapy, and advised to report any lightheadedness or syncope. Additionally, they should avoid potassium supplements or salt substitutes without consulting their physician, and promptly report any signs of infection that may indicate neutropenia. Patients taking hydrochlorothiazide should be instructed to protect their skin from sun exposure and undergo regular skin cancer screenings due to an increased risk of non-melanoma skin cancer associated with the medication.

Postmarketing experience has revealed serious nonfatal adverse events, including an increased risk of non-melanoma skin cancer, particularly squamous cell carcinoma in white patients taking high cumulative doses. Other reported adverse events span various systems, including cardiovascular, digestive, respiratory, and nervous systems, highlighting the need for ongoing monitoring and patient education regarding potential side effects.

FDA Insert (PDF)

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

View full prescribing information (PDF)