Quinapril/Hydrochlorothiazide

Quinapril/Hydrochlorothiazide
	Black Box Warning
	Adult Indications & Dosage
	Pediatric Indications & Dosage
	Contraindications
	Warnings & Precautions
	Adverse Reactions
	Drug Interactions
	Use in Specific Populations
	Administration & Monitoring
	Overdosage
	Pharmacology
	Clinical Studies
	How Supplied
	Images
	Patient Counseling Information
	Precautions with Alcohol
	Brand Names
	Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];

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Black Box Warning

FETAL TOXICITY

See full prescribing information for complete Boxed Warning.

:* When pregnancy is detected, discontinue Quinapril Hydrochloride and Hydrochlorothiazide Tablets as soon as possible.

Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

Overview

Quinapril/Hydrochlorothiazide is an Angiotensin converting enzyme inhibitor, Thiazide diuretic that is FDA approved for the {{{indicationType}}} of hypertension, angioedema. There is a Black Box Warning for this drug as shown here. Common adverse reactions include a list of adverse reactions, separated by commas..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Hypertension

Initial dose : 2.5-40 mg Quinapril hydrochloride (HCl)/ 6.25-25 mg hydrochlorothiazide titrate till over 2-3 weeks to achieve optimum antihypertensive effect 10-80 mg Quinapril HCl/ 12.5 - 50 mg hydrochlorothiazide.

Off-Label Use and Dosage (Adult)

Non–Guideline-Supported Use

Congestive heart failure

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Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Quinapril/Hydrochlorothiazide FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Contraindications

ACCURETIC is contraindicated in patients who are hypersensitive to quinapril or hydrochlorothiazide and in patients with a history of angioedema related to previous treatment with an ACE inhibitor. Because of the hydrochlorothiazide components, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. Do not co-administer aliskiren with ACCURETIC in patients with diabetes.

Warnings

FETAL TOXICITY

See full prescribing information for complete Boxed Warning.

:* When pregnancy is detected, discontinue Quinapril Hydrochloride and Hydrochlorothiazide Tablets as soon as possible.

Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

Anaphylactoid and Possibly Related Reactions

Presumably because angiotensin converting inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including quinapril) may be subject to a variety of adverse reactions, some of them serious.

Head and Neck Angioedema

Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with ACE inhibitors and has been seen in 0.1% of patients receiving quinapril. In two similarly sized US postmarketing quinapril trials that, combined, enrolled over 3,000 black patients and over 19,000 non-blacks, angioedema was reported in 0.30% and 0.55% of blacks (in Study 1 and 2, respectively) and 0.39% and 0.17% of non-blacks. angioedema associated with laryngeal edema can be fatal. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, treatment with ACCURETIC should be discontinued immediately, the patient treated in accordance with accepted medical care, and carefully observed until the swelling disappears. In instances where swelling is confined to the face and lips, the condition generally resolves without treatment; antihistamines may be useful in relieving symptoms. Where there is involvement of the tongue, glottis, or larynx likely to cause airway obstruction, emergency therapy including, but not limited to, subcutaneous epinephrine solution 1:1000 (0.3 to 0.5 mL) should be promptly administered (see PRECAUTIONS and ADVERSE REACTIONS).
Patients taking concomitant mTOR inhibitor (e.g. temsirolimus) therapy may be at increased risk for angioedema.

Intestinal angioedema

Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.

Patients With a History of angioedema

Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see also CONTRAINDICATIONS).

Anaphylactoid Reactions During Desensitization

Two patients undergoing desensitizing treatment with Hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent challenge.

Anaphylactoid Reactions During Membrane Exposure

Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.

Hepatic Failure

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.

Hypotension

ACCURETIC can cause symptomatic hypotension, probably not more frequently than either monotherapy. It was reported in 1.2% of 1,571 patients receiving ACCURETIC during clinical trials. Like other ACE inhibitors, quinapril has been only rarely associated with hypotension in uncomplicated hypertensive patients.
Symptomatic hypotension sometimes associated with oliguria and/or progressive azotemia, and rarely acute renal failure and/or death, include patients with the following conditions or characteristics: heart failure, hyponatremia, high dose diuretic therapy, recent intensive diuresis or increase in diuretic dose, renal dialysis or severe volume and/or salt depletion of any etiology. Volume and/or salt depletion should be corrected before initiating therapy with ACCURETIC.
ACCURETIC should be used cautiously in patients receiving concomitant therapy with other antihypertensives. The thiazide component of ACCURETIC may potentiate the action of other antihypertensive drugs, especially ganglionic or peripheral adrenergic-blocking drugs. The antihypertensive effects of the thiazide component may also be enhanced in the postsympathectomy patients.
In patients at risk of excessive hypotension, therapy with ACCURETIC should be started under close medical supervision. Such patients should be followed closely for the first 2 weeks of treatment and whenever the dosage of quinapril or diuretic is increased. Similar considerations may apply to patients with ischemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in myocardial infarction or cerebrovascular accident.
If excessive hypotension occurs, the patient should be placed in a supine position and, if necessary, treated with intravenous infusion of normal saline. ACCURETIC treatment usually can be continued following restoration of blood pressure and volume. If symptomatic hypotension develops, a dose reduction or discontinuation of ACCURETIC may be necessary.

Impaired Renal Function

ACCURETIC should be used with caution in patients with severe renal disease. thiazides may precipitate azotemia in such patients, and the effects of repeated dosing may be cumulative.
When the renin-angiotensin-aldosterone system is inhibited by quinapril, changes in renal function may be anticipated in susceptible individuals. In patients with severe congestive heart failure, whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin-converting enzyme inhibitors (including quinapril) may be associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death.
In clinical studies in hypertensive patients with unilateral renal artery stenosis, treatment with ACE inhibitors was associated with increases in blood urea nitrogen and serum creatinine; these increases were reversible upon discontinuation of ACE inhibitor, concomitant diuretic, or both. When such patients are treated with ACCURETIC, renal function should be monitored during the first few weeks of therapy.
Some quinapril-treated hypertensive patients with no apparent preexisting renal vascular diseases have developed increases in blood urea nitrogen and serum creatinine, usually minor and transient, especially when quinapril has been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction of ACCURETIC may be required. Evaluation of the hypertensive patients should also include assessment of the renal function (see DOSAGE AND ADMINISTRATION).

Neutropenia/agranulocytosis

Another ACE inhibitor, captopril, has been shown to cause agranulocytosis and bone marrow depression rarely in patients with uncomplicated hypertension, but more frequently in patients with renal impairment, especially if they also have a collagen vascular disease, such as systemic lupus erythematosus or scleroderma. Agranulocytosis did occur during quinapril treatment in one patient with a history of neutropenia during previous captopril therapy. Available data from clinical trials of quinapril are insufficient to show that, in patients without prior reactions to other ACE inhibitors, quinapril does not cause agranulocytosis at similar rates. As with other ACE inhibitors, periodic monitoring of white blood cell counts in patients with collagen vascular disease and/or renal disease should be considered.

Fetal Toxicity

Pregnancy Category D

Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue ACCURETIC as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.

In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue ACCURETIC, unless it is considered life-saving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to ACCURETIC for hypotension, oliguria, and [[hyperkalemia]] (see PRECAUTIONS, Pediatric Use).

Intrauterine exposure to thiazide diuretics is associated with fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that occurred in adults. No teratogenic effects of quinapril were seen in studies of pregnant rats and rabbits. On a mg/kg basis, the doses used were up to 180 times (in rats) and one time (in rabbits) the maximum recommended human dose. No teratogenic effects of ACCURETIC were seen in studies of pregnant rats and rabbits. On a mg/kg (quinapril/hydrochlorothiazide) basis, the doses used were up to 188/94 times (in rats) and 0.6/0.3 times (in rabbits) the maximum recommended human dose.

Impaired Hepatic Function

ACCURETIC should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. Also, since the metabolism of quinapril to quinaprilat is normally dependent upon hepatic esterases, patients with impaired liver function could develop markedly elevated plasma levels of quinapril. No normal pharmacokinetic studies have been carried out in hypertensive patients with impaired liver function.

systemic lupus erythematosus

thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.

Acute Myopia and Secondary Angle-Closure Glaucoma

Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

PRECAUTIONS

General

Derangements of Serum Electrolytes

In clinical trials, hyperkalemia (serum potassium ≥5.8 mmol/L) occurred in approximately 2% of patients receiving quinapril. In most cases, elevated serum potassium levels were isolated values which resolved despite continued therapy. Less than 0.1% of patients discontinued therapy due to hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salt substitutes.

Treatment with thiazide diuretics has been associated with hypokalemia, hyponatremia, and hypochloremic alkalosis. These disturbances have sometimes been manifest as one or more of dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, nausea, and vomiting. Hypokalemia can also sensitize or exaggerate the response of the heart to the toxic effects of digitalis. The risk of hypokalemia is greatest in patients with cirrhosis of the liver, in patients experiencing a brisk diuresis, in patients who are receiving inadequate oral intake of electrolytes, and in patients receiving concomitant therapy with corticosteroids or ACTH. The opposite effects of quinapril and hydrochlorothiazide on serum potassium will approximately balance each other in many patients, so that no net effect upon serum potassium will be seen. In other patients, one or the other effect may be dominant. Initial and periodic determinations of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals.

Chloride deficits secondary to thiazide therapy are generally mild and require specific treatment only under extraordinary circumstances (e.g., in liver disease or renal disease). Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction rather than administration of salt, except in rare instances when the hyponatremia is life threatening. In actual salt depletion, appropriate replacement is the therapy of choice.
Calcium excretion is decreased by thiazides. In a few patients on prolonged thiazide therapy, pathological changes in the parathyroid gland have been observed, with hypercalcemia and hypophosphatemia. More serious complications of hyperparathyroidism (renal lithiasis, bone resorption, and peptic ulceration) have not been seen.
thiazides increase the urinary excretion of magnesium, and hypomagnesemia may result.

Other Metabolic Disturbances

thiazide diuretics tend to reduce glucose tolerance and to raise serum levels of cholesterol, triglycerides, and uric acid. These effects are usually minor, but frank gout or overt diabetes may be precipitated in susceptible patients.

Cough

Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.

Surgery/Anesthesia

In patients undergoing surgery or during anesthesia with agents that produce hypotension, quinapril will block the angiotensin II formation that could otherwise occur secondary to compensatory renin release. Hypotension that occurs as a result of this mechanism can be corrected by volume expansion.