Disclaimer:
Medidex is not a provider of medical services and all information is provided for the convenience of the user. No medical decisions should be made based on the information provided on this website without first consulting a licensed healthcare provider.This website is intended for persons 18 years or older. No person under 18 should consult this website without the permission of a parent or guardian.
Quinapril HCL and Hydrochlorothiazide
Overview
What is Quinapril HCL and Hydrochlorothiazide?
Quinapril Hydrochloride and Hydrochlorothiazide Tablet, USP 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 empirical formula is CHNO. HCl and its structural formula is:
M.W. = 474.98
Quinapril hydrochloride 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 empirical formula is CHCINOS and its structural formula is:
M.W. = 297.72
Hydrochlorothiazide is a white to off-white, crystalline powder which is slightly soluble in water but freely soluble in sodium hydroxide solution.
Quinapril Hydrochloride and Hydrochlorothiazide Tablets, USP are available for oral use as fixed combination tablets in three strengths of quinapril with hydrochlorothiazide: 10 mg with 12.5 mg, 20 mg with 12.5 mg, and 20 mg with 25 mg. Inactive ingredients: 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, xanthan gum.
What does Quinapril HCL and Hydrochlorothiazide look like?
What are the available doses of Quinapril HCL and Hydrochlorothiazide?
Sorry No records found.
What should I talk to my health care provider before I take Quinapril HCL and Hydrochlorothiazide?
Sorry No records found
How should I use Quinapril HCL and Hydrochlorothiazide?
Hypertension:
Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).
Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.
Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.
Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.
This fixed combination is not indicated for the initial therapy of hypertension (see ).
In using Quinapril Hydrochloride and Hydrochlorothiazide Tablets, 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 : ).
Angioedema in Black Patients:
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 ) 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 (eg, 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 Hydrochloride and Hydrochlorothiazide Tablets, 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 Hydrochloride and Hydrochlorothiazide Tablets 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 Hydrochloride and Hydrochlorothiazide Tablets 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 Hydrochloride and Hydrochlorothiazide Tablets 20/25.
Use in Renal Impairment
Regimens of therapy with Quinapril Hydrochloride and Hydrochlorothiazide Tablets need not take account of renal function as long as the patient's creatinine clearance is >30 mL/min/1.73m (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 and Hydrochlorothiazide Tablets are not recommended for use in these patients.
What interacts with Quinapril HCL and Hydrochlorothiazide?
- Quinapril Hydrochloride and Hydrochlorothiazide Tablets are 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 Quinapril Hydrochloride and Hydrochlorothiazide Tablets with aliskiren:
What are the warnings of Quinapril HCL and Hydrochlorothiazide?
Reports of QT prolongation, associated with torsade de pointes (in exceptional cases, fatal), have been received. Caution should be exercised when administering sevoflurane to susceptible patients (e.g.patients with congenital Long QT Syndrome or patients taking drugs that can prolong the QT interval).
Anaphylactoid and Possibly Related Reactions:
Patients taking concomitant mTOR inhibitor (e.g. temsirolimus) therapy may be at increased risk for angioedema.
Intestinal Angioedema:
Anaphylactoid Reactions During Desensitization:
Anaphylactoid Reactions During Membrane Exposure:
Hepatic Failure:
Hypotension:
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 and Hydrochlorothiazide Tablets.
Quinapril Hydrochloride and Hydrochlorothiazide Tablets should be used cautiously in patients receiving concomitant therapy with other antihypertensives. The thiazide component of Quinapril Hydrochloride and Hydrochlorothiazide Tablets 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 and Hydrochlorothiazide Tablets 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 and Hydrochlorothiazide Tablets treatment usually can be continued following restoration of blood pressure and volume. If symptomatic hypotension develops, a dose reduction or discontinuation of Quinapril Hydrochloride and Hydrochlorothiazide Tablets may be necessary.
Impaired Renal Function:
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 and Hydrochlorothiazide Tablets, 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 and Hydrochlorothiazide Tablets may be required. (see ).
Neutropenia/Agranulocytosis:
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 Quinapril Hydrochloride and Hydrochlorothiazide Tablets 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 and Hydrochlorothiazide Tablets, 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 exposure to Quinapril Hydrochloride and Hydrochlorothiazide Tablets for hypotension, oliguria, and hyperkalemia (see ).
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 and Hydrochlorothiazide Tablets were seen in studies of pregnant rats and rabbits. On a mg/kg (Quinapril/hydrochlorothiazide) basis, the doses were up to 188/94 times (in rats) and 0.6/0.3 times (in rabbits) the maximum recommended human dose.
Impaired Hepatic Function:
Systemic Lupus Erythematosus:
Acute Myopia and Secondary Angle-Closure Glaucoma:
What are the precautions of Quinapril HCL and Hydrochlorothiazide?
General
Serum Electrolyte Abnormalities:
Hydrochlorothiazide can cause hypokalemia and hyponatremia. Hypomagnesemia can result in hypokalemia which appears difficult to treat despite potassium repletion. Drugs that inhibit the renin-angiotensin system can cause hyperkalemia. The risk of hyperkalemia may be increased in patients with renal insufficiency, diabetes mellitus or with concomitant use of drugs that raise serum potassium (see ). The risk of hypokalemia may be increased in patients with cirrhosis, brisk diuresis, or with concomitant use of drugs that lower serum potassium. Monitor serum electrolytes periodically.
Other Metabolic Disturbances:
Hydrochlorothiazide may raise the serum uric acid level due to reduced clearance of uric acid and may cause or exacerbate hyperuricemia and precipitate gout in susceptible patients.
Hydrochlorothiazide decreases urinary calcium excretion and may cause elevations of serum calcium. Monitor calcium levels in patients with hypercalcemia receiving Quinapril Hydrochloride and Hydrochlorothiazide Tablets.
Cough:
Surgery/Anesthesia:
Information for Patients
Angioedema:
Pregnancy:
Symptomatic Hypotension:
Tell patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure because of reduction in fluid volume, with the same consequences of lightheadedness and possible syncope.
Tell patients planning to undergo major surgery and/ or general or spinal anesthesia to inform their physicians that they are taking an ACE inhibitor.
Hyperkalemia:
Neutropenia:
NOTE:
Laboratory Tests
The hydrochlorothiazide component of Quinapril Hydrochloride and Hydrochlorothiazide Tablets may decrease serum PBI levels without signs of thyroid disturbance.
Therapy with Quinapril Hydrochloride and Hydrochlorothiazide Tablets should be interrupted for a few days before carrying out tests of parathyroid function.
Drug Interactions
Agents Increasing Serum Potassium:
Lithium:
Dual Blockade of the Renin-Angiotensin System (RAS):
Do not co-administer aliskiren with Quinapril Hydrochloride and Hydrochlorothiazide Tablets in patients with diabetes. Avoid concomitant use of aliskiren with Quinapril Hydrochloride and Hydrochlorothiazide Tablets in patients with renal impairment (GFR<60 mL/min/1.73 m).
Tetracycline and Other Drugs That Interact with Magnesium:
37%, possibly due to the high magnesium content in quinapril tablets. This interaction should be considered if coprescribing quinapril and tetracycline or other drugs that interact with magnesium.
Gold:
Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors
(COX-2 Inhibitors):
The antihypertensive effect of ACE inhibitors, including quinapril may be attenuated by NSAIDs.
Agents that inhibit mTOR:
Other Agents:
Drug interaction studies of quinapril and other agents showed:
When administered concurrently, the following drugs may interact with thiazide diuretics.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity, mutagenicity, and fertility studies have not been conducted in animals with Quinapril Hydrochloride and Hydrochlorothiazide Tablets.
Quinapril hydrochloride was not carcinogenic in mice or rats when given in doses up to 75 or 100 mg/kg/day (50 or 60 times the maximum human daily dose, respectively, on a mg/kg basis and 3.8 or 10 times the maximum human daily dose on a mg/m basis) for 104 weeks. Female rats given the highest dose level had an increased incidence of mesenteric lymph node hemangiomas and skin/subcutaneous lipomas. Neither quinapril nor quinaprilat were mutagenic in the Ames bacterial assay with or without metabolic activation. Quinapril was also negative in the following genetic toxicology studies: mammalian cell point mutation, sister chromatid exchange in cultured mammalian cells, micronucleus test with mice, chromosome aberration with V79 cultured lung cells, and in an cytogenetic study with rat bone marrow. There were no adverse effects on fertility or reproduction in rats at doses up to 100 mg/kg/day (60 and 10 times the maximum daily human dose when based on mg/kg and mg/m, respectively).
Under the auspices of the National Toxicology Program, rats and mice received hydrochlorothiazide in their feed for 2 years, at doses up to 600 mg/kg/day in mice and up to 100 mg/kg/day in rats. These studies uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in rats or female mice, but there was "equivocal" evidence of hepatocarcinogenicity in male mice. Hydrochlorothiazide was not genotoxic in assays using strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 of (the Ames test); in the Chinese hamster ovary (CHO) test for chromosomal aberrations; or assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the sex-linked recessive lethal trait gene. Positive test results were obtained in the CHO sister chromatid exchange (clastogenicity) test and in the mouse lymphoma cell (mutagenicity) assays, using concentrations of hydrochlorothiazide of 43 to 1300 μg/mL. Positive test results were also obtained in the nondisjunction assay, using an unspecified concentration of hydrochlorothiazide.
Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diets, to doses of up to 100 and 4 mg/kg/day, respectively, prior to mating and throughout gestation.
Nursing Mothers
Because quinapril and hydrochlorothiazide are secreted in human milk, caution should be exercised when Quinapril Hydrochloride and Hydrochlorothiazide Tablets are administered to a nursing woman.
Because of the potential for serious adverse reactions in nursing infants from hydrochlorothiazide and the unknown effects of quinapril in infants, a decision should be made whether to discontinue nursing or to discontinue Quinapril Hydrochloride and Hydrochlorothiazide Tablets, taking into account the importance of the drug to the mother.
Geriatric Use
Clinical studies of quinapril HCl/hydrochlorothiazide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Pediatric Use
Neonates with a history of exposure to Quinapril Hydrochloride and Hydrochlorothiazide Tablets:
If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Removal of quinapril, which crosses the placenta, from the neonatal circulation is not significantly accelerated by these means.
Safety and effectiveness of Quinapril Hydrochloride and Hydrochlorothiazide Tablets in children have not been established.
What are the side effects of Quinapril HCL and Hydrochlorothiazide?
Quinapril Hydrochloride and Hydrochlorothiazide Tablets has been evaluated for safety in 1571 patients in controlled and uncontrolled studies. Of these, 498 were given quinapril plus hydrochlorothiazide for at least 1 year, with 153 patients extending combination therapy for over 2 years. In clinical trials with Quinapril Hydrochloride and Hydrochlorothiazide Tablets, no adverse experience specific to the combination has been observed. Adverse experiences that have occurred have been limited to those that have been previously reported with quinapril or hydrochlorothiazide.
Adverse experiences were usually mild and transient, and there was no relationship between side effects and age, sex, race, or duration of therapy. Discontinuation of therapy because of adverse effects was required in 2.1% in patients in controlled studies. The most common reasons for discontinuation of therapy with Quinapril Hydrochloride and Hydrochlorothiazide Tablets were cough (1.0%; see ) and headache (0.7%).
Adverse experiences probably or possibly related to therapy or of unknown relationship to therapy occurring in 1% or more of the 943 patients treated with quinapril plus hydrochlorothiazide in controlled trials are shown below.
Clinical adverse experiences probably, possibly, or definitely related or of uncertain relationship to therapy occurring in ≥0.5% to <1.0% (except as noted) of the patients treated with quinapril/HCTZ in controlled and uncontrolled trials (N=1571) and less frequent, clinically significant events seen in clinical trials or postmarketing experience (the rarer events are in italics) include (listed by body system):
Postmarketing Experience
The following serious nonfatal adverse events, regardless of their relationship to quinapril and HCTZ combination tablets, have been reported during extensive postmarketing experience:
BODY AS A WHOLE: Shock, accidental injury, neoplasm, cellulitis, ascites, generalized edema, hernia and anaphylactoid reaction.
CARDIOVASCULAR SYSTEM: Bradycardia, cor pulmonale, vasculitis, and deep thrombosis.
DIGESTIVE SYSTEM: Gastrointestinal carcinoma, cholestatic jaundice, hepatitis, esophagitis, vomiting, and diarrhea.
EYE DISORDERS: acute myopia and acute angle closure glaucoma (see )
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 petechiases.
SPECIAL SENSES: Abnormal vision.
UROGENITAL SYSTEM: Kidney function abnormal, albuminuria, pyuria, hematuria, and nephrosis.
Quinapril monotherapy has been evaluated for safety in 4960 patients. In clinical trials adverse events which occurred with quinapril were also seen with Quinapril Hydrochloride and Hydrochlorothiazide Tablets. In addition, the following were reported for quinapril at an incidence >0.5%: depression, back pain, constipation, syncope, and amblyopia.
Hydrochlorothiazide has been extensively prescribed for many years, but there has not been enough systematic collection of data to support an estimate of the frequency of the observed adverse reactions. Within organ-system groups, the reported reactions are listed here in decreasing order of severity, without regard to frequency.
Clinical Laboratory Test Findings
Serum Electrolytes:
Creatinine, Blood Urea Nitrogen:
PBI and Tests of Parathyroid Function:
Hematology:
Other
| Percent of Patients in Controlled Trials | ||
| Headache | 6.7 | 30.0 |
| Dizziness | 4.8 | 4.0 |
| Coughing | 3.2 | 2.0 |
| Fatigue | 2.9 | 3.0 |
| Myalgia | 2.4 | 5.0 |
| Viral Infection | 1.9 | 4.0 |
| Rhinitis | 2.0 | 3.0 |
| Nausea and/or Vomiting | 1.8 | 6.0 |
| Abdominal Pain | 1.7 | 4.0 |
| Back Pain | 1.5 | 2.0 |
| Diarrhea | 1.4 | 1.0 |
| Upper Respiratory Infection | 1.3 | 4.0 |
| Insomnia | 1.2 | 2.0 |
| Somnolence | 1.2 | 0.0 |
| Bronchitis | 1.2 | 1.0 |
| Dyspepsia | 1.2 | 2.0 |
| Asthenia | 1.1 | 1.0 |
| Pharyngitis | 1.1 | 2.0 |
| Vasodilatation | 1.0 | 1.0 |
| Vertigo | 1.0 | 2.0 |
| Chest Pain | 1.0 | 2.0 |
| BODY AS A WHOLE: | Asthenia, Malaise | |
| CARDIOVASCULAR: | Palpitation, Tachycardia, | |
| GASTROINTESTINAL: | Mouth or Throat Dry, | |
| NERVOUS/PSYCHIATRIC: | Nervousness, Vertigo, | |
| RESPIRATORY: | Sinusitis, Dyspnea | |
| INTEGUMENTARY: | Pruritus, Sweating Increased, | |
| UROGENITAL SYSTEM: | Acute Renal Failure, Impotence | |
| OTHER: | Agranulocytosis, Thrombocytopenia, Arthralgia | |
| Angioedema: | Angioedema has been reported in 0.1% of patients receiving quinapril (0.1%) (see ). | |
| BODY AS A WHOLE: | Weakness. | |
| CARDIOVASCULAR: | Orthostatic hypotension (may be potentiated by alcohol, barbiturates, or narcotics). | |
| DIGESTIVE: | Pancreatitis, jaundice (intrahepatic cholestatic), sialadenitis, vomiting, diarrhea, cramping, nausea, gastric irritation, constipation, and anorexia. | |
| NEUROLOGIC: | Vertigo, lightheadedness, transient blurred vision, headache, paresthesia, xanthopsia, weakness, and restlessness. | |
| MUSCULOSKELETAL: | Muscle spasm. | |
| HEMATOLOGIC: | Aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, and hemolytic anemia. | |
| RENAL: | Renal failure, renal dysfunction, interstitial nephritis (see ). | |
| METABOLIC: | Hyperglycemia, glycosuria, and hyperuricemia. | |
| HYPERSENSITIVITY: | Necrotizing angiitis, Stevens-Johnson syndrome, respiratory distress (including pneumonitis and pulmonary edema), purpura, urticaria, rash, and photosensitivity. |
What should I look out for while using Quinapril HCL and Hydrochlorothiazide?
Quinapril Hydrochloride and Hydrochlorothiazide Tablets are 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 Quinapril Hydrochloride and Hydrochlorothiazide Tablets with aliskiren:
Anaphylactoid and Possibly Related Reactions:
Head and Neck Angioedema:
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
Patients taking concomitant mTOR inhibitor (e.g. temsirolimus) therapy may be at increased risk for angioedema.
Intestinal Angioedema:
Patients With a History of Angioedema:
Anaphylactoid Reactions During Desensitization:
Anaphylactoid Reactions During Membrane Exposure:
Hepatic Failure:
Hypotension:
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 and Hydrochlorothiazide Tablets.
Quinapril Hydrochloride and Hydrochlorothiazide Tablets should be used cautiously in patients receiving concomitant therapy with other antihypertensives. The thiazide component of Quinapril Hydrochloride and Hydrochlorothiazide Tablets 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 and Hydrochlorothiazide Tablets 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 and Hydrochlorothiazide Tablets treatment usually can be continued following restoration of blood pressure and volume. If symptomatic hypotension develops, a dose reduction or discontinuation of Quinapril Hydrochloride and Hydrochlorothiazide Tablets may be necessary.
Impaired Renal Function:
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 and Hydrochlorothiazide Tablets, 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 and Hydrochlorothiazide Tablets may be required. (see ).
Neutropenia/Agranulocytosis:
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 Quinapril Hydrochloride and Hydrochlorothiazide Tablets 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 and Hydrochlorothiazide Tablets, 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 exposure to Quinapril Hydrochloride and Hydrochlorothiazide Tablets for hypotension, oliguria, and hyperkalemia (see ).
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 and Hydrochlorothiazide Tablets were seen in studies of pregnant rats and rabbits. On a mg/kg (Quinapril/hydrochlorothiazide) basis, the doses were up to 188/94 times (in rats) and 0.6/0.3 times (in rabbits) the maximum recommended human dose.
Impaired Hepatic Function:
Systemic Lupus Erythematosus:
Acute Myopia and Secondary Angle-Closure Glaucoma:
What might happen if I take too much Quinapril HCL and Hydrochlorothiazide?
No specific information is available on the treatment of overdosage with Quinapril Hydrochloride and Hydrochlorothiazide Tablets or quinapril monotherapy; treatment should be symptomatic and supportive. Therapy with Quinapril Hydrochloride and Hydrochlorothiazide Tablets should be discontinued, and the patient should be observed. Dehydration, electrolyte imbalance, and hypotension should be treated by established procedures.
The oral median lethal dose of quinapril/hydrochlorothiazide in combination ranges from 1063/664 to 4640/2896 mg/kg in mice and rats. Doses of 1440 to 4280 mg/kg of quinapril cause significant lethality in mice and rats. In single-dose studies of hydrochlorothiazide, most rats survived doses up to 2.75 g/kg.
Data from human overdoses of ACE inhibitors are scanty; the most likely manifestation of human quinapril overdosage is hypotension. In human hydrochlorothiazide overdose, the most common signs and symptoms observed have been those of dehydration and electrolyte depletion (hypokalemia, hypochloremia, hyponatremia). If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.
Laboratory determinations of serum levels of quinapril and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of quinapril overdose.
No data are available to suggest physiological maneuvers (eg, maneuvers to change the pH of the urine) that might accelerate elimination of quinapril and its metabolites. Hemodialysis and peritoneal dialysis have little effect on the elimination of quinapril and quinaprilat.
Angiotensin II could presumably serve as a specific antagonist-antidote in the setting of quinapril overdose, but angiotensin II is essentially unavailable outside of scattered research facilities. Because the hypotensive effect of quinapril is achieved through vasodilation and effective hypovolemia, it is reasonable to treat quinapril overdose by infusion of normal saline solution.
How should I store and handle Quinapril HCL and Hydrochlorothiazide?
Store at 20° to 25° C (68° to 77° F) [See USP Controlled Room Temperature].Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Store at 20° to 25° C (68° to 77° F) [See USP Controlled Room Temperature].Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Quinapril Hydrochloride and Hydrochlorothiazide Tablets, USP are available in three different strengths:10/12.5 tablets: 20/12.5 tablets: 20/25 tablets: Dispense in tight containers as defined in the USP.Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].Manufactured by:Novel Laboratories, Inc.Somerset, NJ 08873Manufactured for:Lupin Pharmaceuticals, Inc.Baltimore, MD 21202PI7120000205Rev. 05/2016Quinapril Hydrochloride and Hydrochlorothiazide Tablets, USP are available in three different strengths:10/12.5 tablets: 20/12.5 tablets: 20/25 tablets: Dispense in tight containers as defined in the USP.Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].Manufactured by:Novel Laboratories, Inc.Somerset, NJ 08873Manufactured for:Lupin Pharmaceuticals, Inc.Baltimore, MD 21202PI7120000205Rev. 05/2016Quinapril Hydrochloride and Hydrochlorothiazide Tablets, USP are available in three different strengths:10/12.5 tablets: 20/12.5 tablets: 20/25 tablets: Dispense in tight containers as defined in the USP.Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].Manufactured by:Novel Laboratories, Inc.Somerset, NJ 08873Manufactured for:Lupin Pharmaceuticals, Inc.Baltimore, MD 21202PI7120000205Rev. 05/2016Quinapril Hydrochloride and Hydrochlorothiazide Tablets, USP are available in three different strengths:10/12.5 tablets: 20/12.5 tablets: 20/25 tablets: Dispense in tight containers as defined in the USP.Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].Manufactured by:Novel Laboratories, Inc.Somerset, NJ 08873Manufactured for:Lupin Pharmaceuticals, Inc.Baltimore, MD 21202PI7120000205Rev. 05/2016Quinapril Hydrochloride and Hydrochlorothiazide Tablets, USP are available in three different strengths:10/12.5 tablets: 20/12.5 tablets: 20/25 tablets: Dispense in tight containers as defined in the USP.Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].Manufactured by:Novel Laboratories, Inc.Somerset, NJ 08873Manufactured for:Lupin Pharmaceuticals, Inc.Baltimore, MD 21202PI7120000205Rev. 05/2016Quinapril Hydrochloride and Hydrochlorothiazide Tablets, USP are available in three different strengths:10/12.5 tablets: 20/12.5 tablets: 20/25 tablets: Dispense in tight containers as defined in the USP.Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].Manufactured by:Novel Laboratories, Inc.Somerset, NJ 08873Manufactured for:Lupin Pharmaceuticals, Inc.Baltimore, MD 21202PI7120000205Rev. 05/2016Quinapril Hydrochloride and Hydrochlorothiazide Tablets, USP are available in three different strengths:10/12.5 tablets: 20/12.5 tablets: 20/25 tablets: Dispense in tight containers as defined in the USP.Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].Manufactured by:Novel Laboratories, Inc.Somerset, NJ 08873Manufactured for:Lupin Pharmaceuticals, Inc.Baltimore, MD 21202PI7120000205Rev. 05/2016Quinapril Hydrochloride and Hydrochlorothiazide Tablets, USP are available in three different strengths:10/12.5 tablets: 20/12.5 tablets: 20/25 tablets: Dispense in tight containers as defined in the USP.Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].Manufactured by:Novel Laboratories, Inc.Somerset, NJ 08873Manufactured for:Lupin Pharmaceuticals, Inc.Baltimore, MD 21202PI7120000205Rev. 05/2016Quinapril Hydrochloride and Hydrochlorothiazide Tablets, USP are available in three different strengths:10/12.5 tablets: 20/12.5 tablets: 20/25 tablets: Dispense in tight containers as defined in the USP.Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].Manufactured by:Novel Laboratories, Inc.Somerset, NJ 08873Manufactured for:Lupin Pharmaceuticals, Inc.Baltimore, MD 21202PI7120000205Rev. 05/2016Quinapril Hydrochloride and Hydrochlorothiazide Tablets, USP are available in three different strengths:10/12.5 tablets: 20/12.5 tablets: 20/25 tablets: Dispense in tight containers as defined in the USP.Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].Manufactured by:Novel Laboratories, Inc.Somerset, NJ 08873Manufactured for:Lupin Pharmaceuticals, Inc.Baltimore, MD 21202PI7120000205Rev. 05/2016Quinapril Hydrochloride and Hydrochlorothiazide Tablets, USP are available in three different strengths:10/12.5 tablets: 20/12.5 tablets: 20/25 tablets: Dispense in tight containers as defined in the USP.Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].Manufactured by:Novel Laboratories, Inc.Somerset, NJ 08873Manufactured for:Lupin Pharmaceuticals, Inc.Baltimore, MD 21202PI7120000205Rev. 05/2016Quinapril Hydrochloride and Hydrochlorothiazide Tablets, USP are available in three different strengths:10/12.5 tablets: 20/12.5 tablets: 20/25 tablets: Dispense in tight containers as defined in the USP.Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].Manufactured by:Novel Laboratories, Inc.Somerset, NJ 08873Manufactured for:Lupin Pharmaceuticals, Inc.Baltimore, MD 21202PI7120000205Rev. 05/2016Quinapril Hydrochloride and Hydrochlorothiazide Tablets, USP are available in three different strengths:10/12.5 tablets: 20/12.5 tablets: 20/25 tablets: Dispense in tight containers as defined in the USP.Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].Manufactured by:Novel Laboratories, Inc.Somerset, NJ 08873Manufactured for:Lupin Pharmaceuticals, Inc.Baltimore, MD 21202PI7120000205Rev. 05/2016Quinapril Hydrochloride and Hydrochlorothiazide Tablets, USP are available in three different strengths:10/12.5 tablets: 20/12.5 tablets: 20/25 tablets: Dispense in tight containers as defined in the USP.Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature].Manufactured by:Novel Laboratories, Inc.Somerset, NJ 08873Manufactured for:Lupin Pharmaceuticals, Inc.Baltimore, MD 21202PI7120000205Rev. 05/2016
Clinical Information
Chemical Structure
No Image foundClinical Pharmacology
Mechanism of Action:
While the principal mechanism of antihypertensive effect is thought to be through the reninangiotensin-aldosterone system, quinapril exerts antihypertensive actions even in patients with low renin hypertension. Quinapril was an effective antihypertensive in all races studied, although it was somewhat less effective in blacks (usually a predominantly low renin group) than in non-blacks. 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.
Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The reninaldosterone link is mediated by angiotensin, so coadministration of an ACE inhibitor tends to reverse the potassium loss associated with these diuretics.
The mechanism of the antihypertensive effect of thiazides is unknown.
Pharmacokinetics and Metabolism:
The rate of quinapril absorption was reduced by 14% when Quinapril Hydrochloride and Hydrochlorothiazide Tablets were administered with a high-fat meal as compared to fasting, while the extent of absorption was not affected. The rate of hydrochlorothiazide absorption was reduced by 12% when Quinapril Hydrochloride and Hydrochlorothiazide Tablets were administered with a high-fat meal, while the extent of absorption was not significantly affected. Therefore, Quinapril Hydrochloride and Hydrochlorothiazide Tablets may be administered without regard to food.
Following absorption, quinapril is deesterified to its major active metabolite, quinaprilat (about 38% of oral dose), and to other minor inactive metabolites. Following multiple oral dosing of quinapril, there is an effective accumulation half-life of quinaprilat of approximately 3 hours, and peak plasma quinaprilat concentrations are observed approximately 2 hours postdose. Approximately 97% of either quinapril or quinaprilat circulating in plasma is bound to proteins. Hydrochlorothiazide is not metabolized. Its apparent volume of distribution is 3.6 to 7.8 L/kg, consistent with measured plasma protein binding of 67.9%. The drug also accumulates in red blood cells, so that whole blood levels are 1.6 to 1.8 times those measured in plasma.
Some placental passage occurred when quinapril was administered to pregnant rats. Studies in rats indicate that quinapril and its metabolites do not cross the blood-brain barrier.
Hydrochlorothiazide crosses the placenta freely but not the blood-brain barrier.
Quinaprilat is eliminated primarily by renal excretion, up to 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. Hydrochlorothiazide is excreted unchanged by the kidney. When plasma levels have been followed for at least 24 hours, the plasma half-life has been observed to vary between 4 to 15 hours. At least 61% of the oral dose is eliminated unchanged within 24 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 have little effect on the elimination of quinapril and quinaprilat. Elimination of quinaprilat is reduced in elderly patients (≥65 years) and in those with heart failure; this reduction is attributable to decrease in renal function (see ). Quinaprilat concentrations are reduced in patients with alcoholic cirrhosis due to impaired deesterification of quinapril. In a study of patients with impaired renal function (mean creatinine clearance of 19 mL/min), the half-life of hydrochlorothiazide elimination was lengthened to 21 hours.
The pharmacokinetics of quinapril and quinaprilat are linear over a single-dose range of 5- to 80-mg doses and 40- to 160-mg in multiple daily doses.
Pharmacodynamics and Clinical Effects:
Administration of 10 to 80 mg of quinapril to patients with mild to severe hypertension results in a reduction of sitting and standing blood pressure to about the same extent with minimal effect on heart rate. Symptomatic postural hypotension is infrequent, although it can occur in patients who are salt- and/or volume-depleted (see ).
Antihypertensive activity commences within 1 hour with peak effects usually achieved by 2 to 4 hours after dosing. During chronic therapy, most of the blood pressure lowering effect of a given dose is obtained in 1 to 2 weeks. In multiple-dose studies, 10 to 80 mg per day in single or divided doses lowered systolic and diastolic blood pressure throughout the dosing interval, with a trough effect of about 5 to 11/3 to 7 mm Hg. The trough effect represents about 50% of the peak effect.
While the dose-response relationship is relatively flat, doses of 40 to 80 mg were somewhat more effective at trough than 10 to 20 mg, and twice-daily dosing tended to give a somewhat lower trough blood pressure than once-daily dosing with the same total dose. The antihypertensive effect of quinapril continues during long-term therapy, with no evidence of loss of effectiveness.
Hemodynamic assessments in patients with hypertension indicate that 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.
Therapeutic effects of quinapril appear to be the same for elderly (≥65 years of age) and younger adult patients given the same daily dosages, with no increase in adverse events in elderly patients. In patients with hypertension, quinapril 10 to 40 mg was similar in effectiveness to captopril, enalapril, propranolol, and thiazide diuretics.
After oral administration of hydrochlorothiazide, diuresis begins within 2 hours, peaks in about 4 hours, and lasts about 6 to 12 hours. Use of quinapril with a thiazide diuretic gives blood pressure lowering effect greater than that seen with either agent alone. In clinical trials of quinapril/hydrochlorothiazide using quinapril doses of 2.5 to 40 mg and hydrochlorothiazide doses of 6.25 to 25 mg, the antihypertensive effects were sustained for at least 24 hours, and increased with increasing dose of either component. Although quinapril monotherapy is somewhat less effective in blacks than in non-blacks, the efficacy of combination therapy appears to be independent of race. By blocking the renin-angiotensin-aldosterone axis, administration of quinapril tends to reduce the potassium loss associated with the diuretic. In clinical trials of Quinapril Hydrochloride and Hydrochlorothiazide Tablets, the average change in serum potassium was near zero when 2.5 to 40 mg of quinapril was combined with hydrochlorothiazide 6.25 mg, and the average subject who received 10 to 20/12.5 to 25 mg experienced a milder reduction in serum potassium than that experienced by the average subject receiving the same dose of hydrochlorothiazide monotherapy.
Non-Clinical Toxicology
Quinapril Hydrochloride and Hydrochlorothiazide Tablets are 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 Quinapril Hydrochloride and Hydrochlorothiazide Tablets with aliskiren:
Anaphylactoid and Possibly Related Reactions:
Head and Neck Angioedema:
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
Patients taking concomitant mTOR inhibitor (e.g. temsirolimus) therapy may be at increased risk for angioedema.
Intestinal Angioedema:
Patients With a History of Angioedema:
Anaphylactoid Reactions During Desensitization:
Anaphylactoid Reactions During Membrane Exposure:
Hepatic Failure:
Hypotension:
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 and Hydrochlorothiazide Tablets.
Quinapril Hydrochloride and Hydrochlorothiazide Tablets should be used cautiously in patients receiving concomitant therapy with other antihypertensives. The thiazide component of Quinapril Hydrochloride and Hydrochlorothiazide Tablets 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 and Hydrochlorothiazide Tablets 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 and Hydrochlorothiazide Tablets treatment usually can be continued following restoration of blood pressure and volume. If symptomatic hypotension develops, a dose reduction or discontinuation of Quinapril Hydrochloride and Hydrochlorothiazide Tablets may be necessary.
Impaired Renal Function:
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 and Hydrochlorothiazide Tablets, 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 and Hydrochlorothiazide Tablets may be required. (see ).
Neutropenia/Agranulocytosis:
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 Quinapril Hydrochloride and Hydrochlorothiazide Tablets 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 and Hydrochlorothiazide Tablets, 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 exposure to Quinapril Hydrochloride and Hydrochlorothiazide Tablets for hypotension, oliguria, and hyperkalemia (see ).
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 and Hydrochlorothiazide Tablets were seen in studies of pregnant rats and rabbits. On a mg/kg (Quinapril/hydrochlorothiazide) basis, the doses were up to 188/94 times (in rats) and 0.6/0.3 times (in rabbits) the maximum recommended human dose.
Impaired Hepatic Function:
Systemic Lupus Erythematosus:
Acute Myopia and Secondary Angle-Closure Glaucoma:
No untoward clinical manifestations have been observed in limited experience with patients in whom milrinone was used concurrently with the following drugs: digitalis glycosides; lidocaine, quinidine; hydralazine, prazosin; isosorbide dinitrate, nitroglycerin; chlorthalidone, furosemide, hydrochlorothiazide, spironolactone; captopril; heparin, warfarin, diazepam, insulin; and potassium supplements.
Serum Electrolyte Abnormalities:
Hydrochlorothiazide can cause hypokalemia and hyponatremia. Hypomagnesemia can result in hypokalemia which appears difficult to treat despite potassium repletion. Drugs that inhibit the renin-angiotensin system can cause hyperkalemia. The risk of hyperkalemia may be increased in patients with renal insufficiency, diabetes mellitus or with concomitant use of drugs that raise serum potassium (see ). The risk of hypokalemia may be increased in patients with cirrhosis, brisk diuresis, or with concomitant use of drugs that lower serum potassium. Monitor serum electrolytes periodically.
Other Metabolic Disturbances:
Hydrochlorothiazide may raise the serum uric acid level due to reduced clearance of uric acid and may cause or exacerbate hyperuricemia and precipitate gout in susceptible patients.
Hydrochlorothiazide decreases urinary calcium excretion and may cause elevations of serum calcium. Monitor calcium levels in patients with hypercalcemia receiving Quinapril Hydrochloride and Hydrochlorothiazide Tablets.
Cough:
Surgery/Anesthesia:
Information for Patients
Angioedema:
Pregnancy:
Symptomatic Hypotension:
Tell patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure because of reduction in fluid volume, with the same consequences of lightheadedness and possible syncope.
Tell patients planning to undergo major surgery and/ or general or spinal anesthesia to inform their physicians that they are taking an ACE inhibitor.
Hyperkalemia:
Neutropenia:
NOTE:
Laboratory Tests
The hydrochlorothiazide component of Quinapril Hydrochloride and Hydrochlorothiazide Tablets may decrease serum PBI levels without signs of thyroid disturbance.
Therapy with Quinapril Hydrochloride and Hydrochlorothiazide Tablets should be interrupted for a few days before carrying out tests of parathyroid function.
Drug Interactions
Agents Increasing Serum Potassium:
Lithium:
Dual Blockade of the Renin-Angiotensin System (RAS):
Do not co-administer aliskiren with Quinapril Hydrochloride and Hydrochlorothiazide Tablets in patients with diabetes. Avoid concomitant use of aliskiren with Quinapril Hydrochloride and Hydrochlorothiazide Tablets in patients with renal impairment (GFR<60 mL/min/1.73 m).
Tetracycline and Other Drugs That Interact with Magnesium:
37%, possibly due to the high magnesium content in quinapril tablets. This interaction should be considered if coprescribing quinapril and tetracycline or other drugs that interact with magnesium.
Gold:
Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors
(COX-2 Inhibitors):
The antihypertensive effect of ACE inhibitors, including quinapril may be attenuated by NSAIDs.
Agents that inhibit mTOR:
Other Agents:
Drug interaction studies of quinapril and other agents showed:
When administered concurrently, the following drugs may interact with thiazide diuretics.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity, mutagenicity, and fertility studies have not been conducted in animals with Quinapril Hydrochloride and Hydrochlorothiazide Tablets.
Quinapril hydrochloride was not carcinogenic in mice or rats when given in doses up to 75 or 100 mg/kg/day (50 or 60 times the maximum human daily dose, respectively, on a mg/kg basis and 3.8 or 10 times the maximum human daily dose on a mg/m basis) for 104 weeks. Female rats given the highest dose level had an increased incidence of mesenteric lymph node hemangiomas and skin/subcutaneous lipomas. Neither quinapril nor quinaprilat were mutagenic in the Ames bacterial assay with or without metabolic activation. Quinapril was also negative in the following genetic toxicology studies: mammalian cell point mutation, sister chromatid exchange in cultured mammalian cells, micronucleus test with mice, chromosome aberration with V79 cultured lung cells, and in an cytogenetic study with rat bone marrow. There were no adverse effects on fertility or reproduction in rats at doses up to 100 mg/kg/day (60 and 10 times the maximum daily human dose when based on mg/kg and mg/m, respectively).
Under the auspices of the National Toxicology Program, rats and mice received hydrochlorothiazide in their feed for 2 years, at doses up to 600 mg/kg/day in mice and up to 100 mg/kg/day in rats. These studies uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in rats or female mice, but there was "equivocal" evidence of hepatocarcinogenicity in male mice. Hydrochlorothiazide was not genotoxic in assays using strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 of (the Ames test); in the Chinese hamster ovary (CHO) test for chromosomal aberrations; or assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the sex-linked recessive lethal trait gene. Positive test results were obtained in the CHO sister chromatid exchange (clastogenicity) test and in the mouse lymphoma cell (mutagenicity) assays, using concentrations of hydrochlorothiazide of 43 to 1300 μg/mL. Positive test results were also obtained in the nondisjunction assay, using an unspecified concentration of hydrochlorothiazide.
Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diets, to doses of up to 100 and 4 mg/kg/day, respectively, prior to mating and throughout gestation.
Nursing Mothers
Because quinapril and hydrochlorothiazide are secreted in human milk, caution should be exercised when Quinapril Hydrochloride and Hydrochlorothiazide Tablets are administered to a nursing woman.
Because of the potential for serious adverse reactions in nursing infants from hydrochlorothiazide and the unknown effects of quinapril in infants, a decision should be made whether to discontinue nursing or to discontinue Quinapril Hydrochloride and Hydrochlorothiazide Tablets, taking into account the importance of the drug to the mother.
Geriatric Use
Clinical studies of quinapril HCl/hydrochlorothiazide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Pediatric Use
Neonates with a history of exposure to Quinapril Hydrochloride and Hydrochlorothiazide Tablets:
If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. Removal of quinapril, which crosses the placenta, from the neonatal circulation is not significantly accelerated by these means.
Safety and effectiveness of Quinapril Hydrochloride and Hydrochlorothiazide Tablets in children have not been established.
Quinapril Hydrochloride and Hydrochlorothiazide Tablets has been evaluated for safety in 1571 patients in controlled and uncontrolled studies. Of these, 498 were given quinapril plus hydrochlorothiazide for at least 1 year, with 153 patients extending combination therapy for over 2 years. In clinical trials with Quinapril Hydrochloride and Hydrochlorothiazide Tablets, no adverse experience specific to the combination has been observed. Adverse experiences that have occurred have been limited to those that have been previously reported with quinapril or hydrochlorothiazide.
Adverse experiences were usually mild and transient, and there was no relationship between side effects and age, sex, race, or duration of therapy. Discontinuation of therapy because of adverse effects was required in 2.1% in patients in controlled studies. The most common reasons for discontinuation of therapy with Quinapril Hydrochloride and Hydrochlorothiazide Tablets were cough (1.0%; see ) and headache (0.7%).
Adverse experiences probably or possibly related to therapy or of unknown relationship to therapy occurring in 1% or more of the 943 patients treated with quinapril plus hydrochlorothiazide in controlled trials are shown below.
Clinical adverse experiences probably, possibly, or definitely related or of uncertain relationship to therapy occurring in ≥0.5% to <1.0% (except as noted) of the patients treated with quinapril/HCTZ in controlled and uncontrolled trials (N=1571) and less frequent, clinically significant events seen in clinical trials or postmarketing experience (the rarer events are in italics) include (listed by body system):
Postmarketing Experience
The following serious nonfatal adverse events, regardless of their relationship to quinapril and HCTZ combination tablets, have been reported during extensive postmarketing experience:
BODY AS A WHOLE: Shock, accidental injury, neoplasm, cellulitis, ascites, generalized edema, hernia and anaphylactoid reaction.
CARDIOVASCULAR SYSTEM: Bradycardia, cor pulmonale, vasculitis, and deep thrombosis.
DIGESTIVE SYSTEM: Gastrointestinal carcinoma, cholestatic jaundice, hepatitis, esophagitis, vomiting, and diarrhea.
EYE DISORDERS: acute myopia and acute angle closure glaucoma (see )
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 petechiases.
SPECIAL SENSES: Abnormal vision.
UROGENITAL SYSTEM: Kidney function abnormal, albuminuria, pyuria, hematuria, and nephrosis.
Quinapril monotherapy has been evaluated for safety in 4960 patients. In clinical trials adverse events which occurred with quinapril were also seen with Quinapril Hydrochloride and Hydrochlorothiazide Tablets. In addition, the following were reported for quinapril at an incidence >0.5%: depression, back pain, constipation, syncope, and amblyopia.
Hydrochlorothiazide has been extensively prescribed for many years, but there has not been enough systematic collection of data to support an estimate of the frequency of the observed adverse reactions. Within organ-system groups, the reported reactions are listed here in decreasing order of severity, without regard to frequency.
Clinical Laboratory Test Findings
Serum Electrolytes:
Creatinine, Blood Urea Nitrogen:
PBI and Tests of Parathyroid Function:
Hematology:
Other
Reference
This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"
While we update our database periodically, we cannot guarantee it is always updated to the latest version.
Review
Read user comments about the side effects, benefits, and effectiveness of losartan oral.
Overall User Ratings
515Total User Reviews
User Reviews
Learn about
User Reviews
Professional
Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72Tips
Tips
Interactions
Interactions
A total of 440 drugs (1549 brand and generic names) are known to interact with Imbruvica (ibrutinib). 228 major drug interactions (854 brand and generic names) 210 moderate drug interactions (691 brand and generic names) 2 minor drug interactions (4 brand and generic names) Show all medications in the database that may interact with Imbruvica (ibrutinib).