Quinapril-Hydrochlorothiazide (quinapril HCl/hydrochlorothiazide)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Hydrochlorothiazide is a thiazide diuretic and antihypertensive agent.
Quinapril is a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor.
Quinapril is an angiotensin-converting enzyme (ACE) inhibitor. Quinapril undergoes de-esterification to form its active metabolite, quinaprilat, which inhibits ACE activity in both humans and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor, angiotensin II.
The therapeutic effects of quinapril in hypertension and heart failure are attributed primarily to inhibition of circulating and tissue ACE, resulting in reduced formation of angiotensin II. Quinapril attenuates increases in blood pressure induced by intravenously administered angiotensin I but does not affect the pressor responses to angiotensin II, norepinephrine, or epinephrine.
Angiotensin II also stimulates aldosterone secretion from the adrenal cortex, promoting renal sodium and fluid reabsorption. Reduced aldosterone secretion by quinapril may result in a small increase in serum potassium. In controlled clinical trials in patients with hypertension, treatment with quinapril alone resulted in mean increases in serum potassium of 0.07 mmol/L.
Inhibition of angiotensin II-mediated negative feedback on renin release results in increased plasma renin activity. ACE is identical to kininase II, an enzyme that degrades bradykinin, a potent peptide vasodilator; whether increased levels of bradykinin play a role in the therapeutic effect of quinapril remains to be elucidated.
Although the antihypertensive effect of quinapril is primarily mediated through modulation of the renin-angiotensin-aldosterone system, blood pressure reduction with quinapril has also been observed in patients with low-renin hypertension. Quinapril demonstrated antihypertensive efficacy across all racial groups studied; however, it was somewhat less effective in Blacks (usually a predominantly low renin group) than in non-Blacks.
Antihypertensive activity of quinapril commences within 1 hour, with peak blood pressure reduction effects usually achieved by 2-4 hours after dosing. During chronic therapy, most of the blood pressure lowering effect of a given dose is obtained in 1-2 weeks. A single 20-mg dose of quinapril produces >80% inhibition of plasma ACE for a duration of 24 hours.
The suppression of the pressor response to angiotensin I is of shorter duration; following a 20 mg dose, inhibition is approximately 75% at 4 hours, 50% at 8 hours, and declines to about 20% at 24 hours. In contrast, with chronic administration, doses ranging from 20-80 mg result in substantial inhibition of angiotensin II levels at 24 hours.
Blood pressure reduction produced by quinapril is accompanied by a reduction in total peripheral resistance and renal vascular resistance with little or no change in heart rate, cardiac index, renal blood flow, glomerular filtration rate, or filtration fraction. Use of quinapril with a thiazide diuretic gives a blood-pressure lowering effect greater than that seen with either agent alone. Therapeutic effects appear to be the same for geriatric patients (>=65 years of age) and younger adult patients given the same daily dosages, with no increase in adverse events in geriatric patients.
In patients with heart failure treated with digitalis and diuretics, parenteral quinaprilat, the active metabolite of quinapril, reduced pulmonary capillary wedge pressure and systemic vascular resistance and increased cardiac output/index. Similar favorable hemodynamic effects were observed with oral quinapril in baseline-controlled trials, and such effects appeared to be maintained during chronic oral quinapril therapy. Quinapril reduced renal hepatic vascular resistance and increased renal and hepatic blood flow with glomerular filtration rate remaining unchanged.
Improvements in severity and symptoms of heart failure were evident after 6 months of treatment and maintained for up to 2 years of quinapril therapy. The effects of quinapril on long-term mortality in heart failure have not been evaluated.
Following oral administration, peak plasma quinapril concentrations are observed within 1 hour. The extent of absorption is >=60%. The rate and extent of quinapril absorption are diminished moderately (approximately 25-30%) when quinapril tablets are administered during a high-fat meal.
Following absorption, quinapril is de-esterified to its major active metabolite, quinaprilat (about 38% of an oral dose), and to other minor inactive metabolites. Peak plasma quinaprilat concentrations are observed approximately 2 hours post-dose. Quinaprilat concentrations are reduced in patients with alcoholic cirrhosis due to impaired de-esterification of quinapril.
Studies in rats indicate that quinapril and its metabolites do not cross the blood-brain barrier.
Approximately 97% of either quinapril or quinaprilat circulating in plasma is bound to proteins. Quinaprilat is eliminated primarily by renal excretion (<=96% of an IV dose) and has an elimination half-life in plasma of approximately 2 hours and a prolonged terminal phase with a half-life of 25 hours. In patients with renal insufficiency, the elimination half-life of quinaprilat increases as creatinine clearance decreases.
There is a linear correlation between plasma quinaprilat clearance and creatinine clearance. In patients with end-stage renal disease, chronic hemodialysis or continuous ambulatory peritoneal dialysis has little effect on the elimination of quinapril and quinaprilat. Elimination of quinaprilat may be reduced in geriatric patients (>=65 years) and in those with heart failure; this reduction is attributable to decrease in renal function.
USES: This medication is used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. This product contains 2 medications, quinapril and hydrochlorothiazide.
Quinapril belongs to a class of drugs known as ACE inhibitors. It works by relaxing blood vessels so blood can flow more easily. Hydrochlorothiazide is a "water pill" (diuretic) that causes you to make more urine.
This helps your body get rid of extra water and salt.
Generic name: quinapril HCl/hydrochlorothiazide
Pronunciation: (KWIN-a-pril/HYE-droe-KLOR-oh-THYE-a-zide)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Quinapril-Hydrochlorothiazide
Indications
The following indications are listed for Quinapril-Hydrochlorothiazide:
- Hypertension
Also known as: Elevated Blood Pressure, Essential Hypertension, Hyperpiesia, Hyperpiesis, Hypertensive Disorder, Systemic Arterial Hypertension.
Dosing
Dosage of hydrochlorothiazide should be individualized according to the patient's requirements and response. The lowest dosage necessary to produce the desired clinical effect should be used. If hydrochlorothiazide is added to the regimen of a patient stabilized on a potent hypotensive agent, dosage of the hypotensive agent should initially be reduced to avoid the possibility of severe hypotension.
Dosage of quinapril hydrochloride is expressed in terms of quinapril.
Dosage of quinapril must be adjusted according to patient tolerance and response.
In patients at risk for excessive hypotension, start quinapril therapy under close medical supervision and follow patients closely for at least 2 weeks after initiation of therapy or whenever the dosage of quinapril and/or a diuretic is increased.
Hydrochlorothiazide is administered orally.
Quinapril is administered orally once or twice daily. The antihypertensive effect may diminish toward the end of the dosing interval and can be addressed in some patients with twice daily dosing.
Quinapril hydrochloride is commercially available as tablets containing 5 mg, 10 mg, 20 mg, or 40 mg of quinapril.
Quinapril hydrochloride is also commercially available in fixed combination with hydrochlorothiazide. See the full prescribing information for administration of this fixed-combination product.
Store quinapril tablets at 20-25degreesC. Protect from light.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Known hypersensitivity (e.g., history of angioedema) to quinapril, other angiotensin-converting enzyme (ACE) inhibitors, or any ingredient in the formulation.
*Concomitant aliskiren therapy in patients with diabetes mellitus.
*Concomitant use (within 36 hours) of a neprilysin inhibitor (e.g., sacubitril).
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in clinical trials in at least 1% of patients receiving quinapril for the management of hypertension include headache, dizziness, fatigue, cough, nausea and/or vomiting, and abdominal pain.
Adverse effects reported in at least 1% of patients receiving quinapril for the management of heart failure include dizziness, cough, fatigue, nausea and/or vomiting, chest pain, hypotension, dyspnea, diarrhea, headache, myalgia, rash, back pain, increased serum creatinine concentration, and increased BUN.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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The safety and efficacy of quinapril in pediatric patients have not been established.
If oliguria or hypotension occurs in neonates with a history of in utero exposure to quinapril, support blood pressure and renal function. Exchange transfusions or dialysis may be required. Removal of quinapril, which crosses the placenta, from the neonatal circulation is not significantly accelerated by these means.
Drugs that act on the renin-angiotensin system (e.g., ACE inhibitors, angiotensin II receptor antagonists) reduce fetal renal function and increase fetal and neonatal morbidity and mortality when used in pregnancy during the second and third trimesters. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal effects include skull hypoplasia, anuria, hypotension, renal failure, and death. No teratogenic effects of quinapril were observed in animal studies.
Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both the mother and fetus. Discontinue quinapril as soon as possible when pregnancy is detected. In the rare situation that use of quinapril is deemed necessary, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intraamniotic environment. Fetal testing may be appropriate, based on the week of pregnancy; however, oligohydramnios may not appear until after the fetus has sustained irreversible injury. If oligohydramnios is observed, discontinue quinapril unless it is considered lifesaving for the mother. Closely observe infants with histories of in utero exposure to quinapril for hypotension, oliguria, and hyperkalemia.
Quinapril is distributed into milk in humans. Exercise caution if quinapril is administered to a nursing woman.
The recommended initial dosage of quinapril in geriatric patients (>=65 years of age) is 10 mg once daily with careful titration and close blood pressure monitoring.
Data from clinical studies evaluating quinapril in individuals 65 years of age and older are insufficient to determine whether geriatric patients respond differently than younger adults. Other reported clinical experience has not identified differences in responses between geriatric and younger patients. Peak plasma concentrations and AUC of quinaprilat, a major metabolite of quinapril, were increased in geriatric patients compared with values observed in younger patients, but these differences appeared to be related to decreased renal function in geriatric patients; no pharmacokinetic differences related solely to age were observed.
Because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy in geriatric patients, initiate dosages of quinapril at the lower end of the usual dosage range in such patients. Because geriatric patients are more likely to have decreased renal function, it may be useful to monitor renal function.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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