Quinapril Hydrochloride/hydrochlorothiazide
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Questions & Answers
Side Effects & Adverse Reactions
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 0.3% 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 quinapril hydrochloride/hydrochlorothiazide 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).
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
Quinapril hydrochloride/hydrochlorothiazide can cause symptomatic hypotension, probably not more frequently than either monotherapy. It was reported in 1.2% of 1,571 patients receiving quinapril hydrochloride/hydrochlorothiazide 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 quinapril hydrochloride/hydrochlorothiazide.
Quinapril hydrochloride/hydrochlorothiazide should be used cautiously in patients receiving concomitant therapy with other antihypertensives. The thiazide component of quinapril hydrochloride/hydrochlorothiazide 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 quinapril hydrochloride/hydrochlorothiazide 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. Quinapril hydrochloride/hydrochlorothiazide treatment usually can be continued following restoration of blood pressure and volume. If symptomatic hypotension develops, a dose reduction or discontinuation of quinapril hydrochloride/hydrochlorothiazide may be necessary.
Impaired Renal Function
Quinapril hydrochloride/hydrochlorothiazide 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 quinapril hydrochloride/hydrochlorothiazide, 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 quinapril hydrochloride/hydrochlorothiazide may be required. Evaluation of the hypertensive patients should also include assessment of the renal function (see DOSAGE AND ADMINISTRATION).
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.
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 quinapril hydrochloride/hydrochlorothiazide 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 quinapril hydrochloride/hydrochlorothiazide, 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 quinapril hydrochloride/hydrochlorothiazide 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 quinapril hydrochloride/hydrochlorothiazide 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
Quinapril hydrochloride/hydrochlorothiazide 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.
Legal Issues
There is currently no legal information available for this drug.
FDA Safety Alerts
There are currently no FDA safety alerts available for this drug.
Manufacturer Warnings
There is currently no manufacturer warning information available for this drug.
FDA Labeling Changes
There are currently no FDA labeling changes available for this drug.
Uses
Quinapril hydrochloride/hydrochlorothiazide tablets are indicated for the treatment of hypertension. This fixed combination is not indicated for the initial therapy of hypertension (see DOSAGE AND ADMINISTRATION).
In using quinapril hydrochloride/hydrochlorothiazide, consideration should be given to the fact that another angiotensin-converting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen-vascular disease. Available data are insufficient to show that quinapril does not have a similar risk (see WARNINGS: Neutropenia/Agranulocytosis).
Angioedema in Black Patients
Black patients receiving ACE inhibitor monotherapy have been reported to have a higher incidence of angioedema compared to non-blacks. It should also be noted that in controlled clinical trials, ACE inhibitors have an effect on blood pressure that is less in black patients than in non-blacks.
History
There is currently no drug history available for this drug.
Other Information
Quinapril hydrochloride/hydrochlorothiazide is a fixed-combination tablet that combines an angiotensin-converting enzyme (ACE) inhibitor, quinapril hydrochloride, and a thiazide diuretic, hydrochlorothiazide.
Quinapril hydrochloride is chemically described as [3S-[2[R*(R*)], 3R*]]-2-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid, monohydrochloride. Its molecular formula is C25H30N2O5. HCl and its structural formula is:
Quinapril hydrochloride USP is a white to off-white amorphous powder that is freely soluble in aqueous solvents.
Hydrochlorothiazide is chemically described as: 6-Chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its molecular formula is C7H8CIN3O4S2 and its structural formula is:
Hydrochlorothiazide USP is a white to off-white, crystalline powder which is slightly soluble in water but freely soluble in sodium hydroxide solution.
Quinapril hydrochloride/hydrochlorothiazide is available for oral use as fixed combination tablets in three strengths of quinapril with hydrochlorothiazide: 10 mg with 12.5 mg (quinapril hydrochloride/hydrochlorothiazide 10/12.5), 20 mg with 12.5 mg (quinapril hydrochloride/hydrochlorothiazide 20/12.5), and 20 mg with 25 mg (quinapril hydrochloride/hydrochlorothiazide20/25). The strength of the quinapril hydrochloride component is in terms of quinapril. Inactive ingredients: lactose monohydrate, magnesium carbonate, crospovidone, povidone, magnesium stearate, hypromellose, hydroxypropyl cellulose, polyethylene glycol 400, titanium dioxide, iron oxide red and iron oxide yellow.
Sources
Quinapril Hydrochloride/hydrochlorothiazide Manufacturers
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Lake Erie Medical Dba Quality Care Products Llc
![Quinapril Hydrochloride/hydrochlorothiazide Tablet, Film Coated [Lake Erie Medical Dba Quality Care Products Llc]](/wp-content/themes/bootstrap/assets/img/loading2.gif)
Quinapril Hydrochloride/hydrochlorothiazide | Lake Erie Medical Dba Quality Care Products Llc
As individual monotherapy, quinapril is an effective treatment of hypertension in once-daily doses of 10 to 80 mg and hydrochlorothiazide is effective in doses of 12.5 to 50 mg. In clinical trials of quinapril/hydrochlorothiazide combination therapy using quinapril doses of 2.5 to 40 mg and hydrochlorothiazide doses of 6.25 to 25 mg, the antihypertensive effects increased with increasing dose of either component.
The side effects (see WARNINGS) of quinapril are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of quinapril and hydrochlorothiazide will be associated with both sets of dose-independent side effects, but regimens that combine low doses of hydrochlorothiazide with quinapril produce minimal effects on serum potassium. In clinical trials of quinapril/hydrochlorothiazide, the average change in serum potassium was near zero in subjects who received HCTZ 6.25 mg in the combination, and the average subject who received 10 to 40/12.5 to 25 mg experienced a milder reduction in serum potassium than that experienced by the average subject receiving the same dose of hydrochlorothiazide monotherapy.
To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.
Therapy Guided by Clinical Effect
Patients whose blood pressures are not adequately controlled with quinapril monotherapy may instead be given quinapril/hydrochlorothiazide 10/12.5 or 20/12.5. Further increases of either or both components could depend on clinical response. The hydrochlorothiazide dose should generally not be increased until 2 to 3 weeks have elapsed. Patients whose blood pressures are adequately controlled with 25 mg of daily hydrochlorothiazide, but who experience significant potassium loss with this regimen, may achieve blood pressure control with less electrolyte disturbance if they are switched to quinapril/hydrochlorothiazide 10/12.5 or 20/12.5.
Replacement Therapy
For convenience, patients who are adequately treated with 20 mg of quinapril and 25 mg of hydrochlorothiazide and experience no significant electrolyte disturbances may instead wish to receive quinapril/hydrochlorothiazide 20/25.
Use in Renal Impairment
Regimens of therapy with quinapril hydrochloride/hydrochlorothiazide tablets need not take account of renal function as long as the patient’s creatinine clearance is >30 mL/min/ 1.73 m2 (serum creatinine roughly ≤3 mg/dL or 265 µmol/L). In patients with more severe renal impairment, loop diuretics are preferred to thiazides. Therefore, quinapril hydrochloride/hydrochlorothiazide tablets are not recommended for use in these patients. -
Aurobindo Pharma Limited
Quinapril Hydrochloride/hydrochlorothiazide | Sandoz Inc
2.1Usual DosageTreatment with Bupropion Hydrochloride Extended-Release Tablets, USP (SR) should be initiated before the patient’s planned quit day, while the patient is still smoking, because it takes approximately 1 week of treatment to achieve steady-state blood levels of bupropion. The patient should set a “target quit date” within the first 2 weeks of treatment with Bupropion Hydrochloride Extended-Release Tablets, USP (SR).
Dosing
To minimize the risk of seizure:
• Begin dosing with one 150-mg tablet per day for 3 days. • Increase dose to 300 mg/day given as one 150-mg tablet twice each day with an interval of at least 8 hours between each dose. • Do not exceed 300 mg/day.Bupropion Hydrochloride Extended-Release Tablets, USP (SR) should be swallowed whole and not crushed, divided, or chewed, as this may lead to an increased risk of adverse effects including seizures [see WARNINGS AND PRECAUTIONS (5.3)].
Bupropion Hydrochloride Extended-Release Tablets, USP (SR) may be taken with or without food [see CLINICAL PHARMACOLOGY (12.3)].
2.2 Duration of TreatmentTreatment with Bupropion Hydrochloride Extended-Release Tablets, USP (SR) should be continued for 7 to 12 weeks. If the patient has not quit smoking after 7 to 12 weeks, it is unlikely that he or she will quit during that attempt so treatment with Bupropion Hydrochloride Extended-Release Tablets, USP (SR) should probably be discontinued and the treatment plan reassessed. The goal of therapy with Bupropion Hydrochloride Extended-Release Tablets, USP (SR) is complete abstinence.
Discuss discontinuing treatment with Bupropion Hydrochloride Extended-Release Tablets, USP (SR) after 12 weeks if the patient feels ready but consider whether the patient may benefit from ongoing treatment. Patients who successfully quit after 12 weeks of treatment but do not feel ready to discontinue treatment should be considered for ongoing therapy with Bupropion Hydrochloride Extended-Release Tablets, USP (SR); longer treatment should be guided by the relative benefits and risks for individual patients.
It is important that patients continue to receive counseling and support throughout treatment with Bupropion Hydrochloride Extended-Release Tablets, USP (SR) and for a period of time thereafter.
2.3 Individualization of TherapyPatients are more likely to quit smoking and remain abstinent if they are seen frequently and receive support from their physicians or other healthcare professionals. It is important to ensure that patients read the instructions provided to them and have their questions answered. Physicians should review the patient’s overall smoking cessation program that includes treatment with Bupropion Hydrochloride Extended-Release Tablets, USP (SR). Patients should be advised of the importance of participating in the behavioral interventions, counseling, and/or support services to be used in conjunction with Bupropion Hydrochloride Extended-Release Tablets, USP (SR) [see MEDICATION GUIDE].
Patients who fail to quit smoking during an attempt may benefit from interventions to improve their chances for success on subsequent attempts. Patients who are unsuccessful should be evaluated to determine why they failed. A new quit attempt should be encouraged when factors that contributed to failure can be eliminated or reduced, and conditions are more favorable.
2.4 MaintenanceTobacco dependence is a chronic condition. Some patients may need on-going treatment. Whether to continue treatment with Bupropion Hydrochloride Extended-Release Tablets, USP (SR) for periods longer than 12 weeks for smoking cessation must be determined for individual patients.
2.5Combination Treatment with Bupropion Hydrochloride Extended-Release Tablets, USP (SR) and a Nicotine Transdermal System (NTS)Combination treatment with Bupropion Hydrochloride Extended-Release Tablets, USP (SR) and NTS may be prescribed for smoking cessation. The prescriber should review the complete prescribing information for both Bupropion Hydrochloride Extended-Release Tablets, USP (SR) and NTS before using combination treatment [see CLINICAL STUDIES (14)]. Monitoring for treatment-emergent hypertension in patients treated with the combination of Bupropion Hydrochloride Extended-Release Tablets, USP (SR) and NTS is recommended.
2.6Dose Adjustment for Patients with Hepatic ImpairmentIn patients with moderate to severe hepatic impairment (Child-Pugh score: 7 to 15), the maximum dose should not exceed 150 mg every other day. In patients with mild hepatic impairment (Child-Pugh score: 5 to 6), consider reducing the dose and/or frequency of dosing [see USE IN SPECIFIC POPULATIONS (8.7), CLINICAL PHARMACOLOGY (12.3)].
2.7Dose Adjustment for Patients with Renal ImpairmentConsider reducing the dose and/or frequency of Bupropion Hydrochloride Extended-Release Tablets, USP (SR) in patients with renal impairment (Glomerular Filtration Rate less than 90 mL/min) [see USE IN SPECIFIC POPULATIONS (8.6) and CLINICAL PHARMACOLOGY (12.3)].
2.8 Use of Bupropion Hydrochloride Extended-Release Tablets, USP (SR) with Reversible MAOIs Such as Linezolid or Methylene BlueDo not start Bupropion Hydrochloride Extended-Release Tablets, USP (SR) in a patient who is being treated with a reversible MAOI such as linezolid or intravenous methylene blue. Drug interactions can increase the risk of hypertensive reactions [see CONTRAINDICATIONS (4), DRUG INTERACTIONS (7.6)].
In some cases, a patient already receiving therapy with Bupropion Hydrochloride Extended-Release Tablets, USP (SR) may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks or hypertensive reactions in a particular patient, Bupropion Hydrochloride Extended-Release Tablets, USP (SR) should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with Bupropion Hydrochloride Extended-Release Tablets, USP (SR) may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue.
The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with Bupropion Hydrochloride Extended-Release Tablets, USP (SR) is unclear. The clinician should, nevertheless, be aware of the possibility of a drug interaction with such use [see CONTRAINDICATIONS (4) and DRUG INTERACTIONS (7.6)].
![Quinapril Hydrochloride/hydrochlorothiazide Tablet, Film Coated [Aurobindo Pharma Limited]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=b0db1d35-a508-4c4d-b3e9-8963c7f5f4cc&name=cfc51f05-b234-47be-a110-8face53ed887-02.jpg)
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