Thursday, September 29, 2016

Capoten


Generic Name: Captopril
Class: Angiotensin-Converting Enzyme Inhibitors
VA Class: CV800
CAS Number: 62571-86-2



  • May cause fetal and neonatal morbidity and mortality if used during pregnancy.401 402 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)




  • If pregnancy is detected, discontinue captopril as soon as possible.115 402




Introduction

Sulfhydryl ACE inhibitor.1 3 4 5


Uses for Capoten


Hypertension


Management of hypertension (alone or in combination with other classes of antihypertensive agents).100 115 215 259 316 317


One of several preferred initial therapies in hypertensive patients with heart failure, postmyocardial infarction, high coronary disease risk, diabetes mellitus, chronic renal failure, and/or cerebrovascular disease.382


Can be used as monotherapy for initial management of uncomplicated hypertension;115 however, thiazide diuretics are preferred by JNC 7.382


Nephropathy


Stabilization or improvement of effective renal blood flow and glomerular filtration rate and reduction of proteinuria in hypertensive115 141 142 143 174 187 188 189 281 323 or normotensive115 162 patients with moderately impaired renal function,141 143 174 323 moderate to severe renal disease,141 323 or diabetic nephropathy.141 142 143 187 188 189 268 334


CHF


Management of symptomatic CHF, usually in conjunction with cardiac glycosides, diuretics, and β-adrenergic blocking agents.115 210 246 247 248 249 250 252 253 254 256 257 292 304 319 320 321 333 377


Left Ventricular Dysfunction after AMI


Treatment of clinically stable patients with left ventricular dysfunction (ejection fraction ≤40%) to improve survival following MI and to reduce the incidence of overt heart failure and subsequent hospitalizations for CHF.115 319 321 374


Capoten Dosage and Administration


Administration


Oral Administration


Administer orally 1 hour before meals to maximize absorption.115


Dosage


Pediatric Patients


Hypertension

Oral

Dosage has been reduced in proportion to body weight; titrate carefully.115 Some experts recommend an initial dosage of 0.9–1.5 mg/kg daily (given as 0.3–0.5 mg/kg 3 times daily).398 Increase dosage as necessary to a maximum of 6 mg/kg daily.398


Adults


Hypertension

Oral

Initially, 25 mg 2 or 3 times daily.115 316 382 If BP is not adequately controlled after 1–2 weeks, increase dosage to 50 mg 2 or 3 times daily.115


Lower initial dosages (e.g., 6.25 mg twice daily to 12.5 mg 3 times daily) may be effective in some patients, particularly those already receiving a diuretic.a (See Hypotension under Cautions.)


Usual dosage: Manufacturers recommend 25–150 mg 2 or 3 times daily (usually not necessary to exceed 450 mg daily).115 316 JNC 7 recommends 25–100 mg daily given in 2 divided doses; JNC 7 recommends adding another drug, if needed, rather than continuing to increase dosage.382


If combination therapy is initiated with captopril/hydrochlorothiazide fixed-combination preparation, captopril 25 mg and hydrochlorothiazide 15 mg daily initially;102 259 adjust dosage (generally at 6-week intervals) by administering each drug separately or by advancing the fixed-combination preparation.102 259


Hypertensive Crises

Oral

25 mg 2 or 3 times daily, initiated promptly under close supervision with frequent monitoring of BP.115 May continue previous diuretic therapy, but discontinue other hypotensive agents.115 May increase dosage at intervals of ≤24 hours under continuous supervision until optimum BP response is attained or 450 mg daily is given.115 Adjunctive therapy with other hypotensive agents may be necessary.a


Acute therapy (e.g., 12.5–25 mg, repeated once or twice if necessary at intervals of 30–60 minutes or longer) has been effective231 232 236 259 in adults with hypertensive urgencies231 232 259 and emergencies.233 234 235 236 237 238 259 310


Nephropathy

Diabetic Nephropathy

Oral

25 mg 3 times daily.115 262


CHF

Oral

Manufacturers recommend initial dosage of 25 mg 3 times daily;115 in patients with normal or low BP who may be volume- and/or salt-depleted, initial dosage of 6.25 or 12.5 mg 3 times daily.115 Increase dosage gradually to 50 mg 3 times daily; delay further dosage increases for ≥2 weeks to assess response.115


Some clinicians recommend initial dosage of 6.25 or 12.5 mg 3 times daily, with gradual titration over several weeks to 50 mg 3 times daily, regardless of BP, salt/volume status, or concomitant diuretic therapy.321 333 377 Generally titrate dosage to prespecified target (i.e., ≥150 mg daily) or highest tolerated dosage rather than according to response.333 377


Left Ventricular Dysfunction after AMI

Oral

Manufacturers recommend initiation of therapy ≥3 days post-MI with single dose of 6.25 mg, followed by 12.5 mg 3 times daily.115 Increase dosage over next several days to 25 mg 3 times daily and then over next several weeks (as tolerated) to 50 mg 3 times daily.115


Some clinicians recommend initiation of therapy <24 hours post-MI with initial dose of 6.25 mg, followed by 12.5 mg 2 hours later, 25 mg 10–12 hours later, and then 50 mg twice daily as tolerated.319 Recommended maintenance dosage: 50 mg 3 times daily.115


Prescribing Limits


Pediatric Patients


Hypertension

Oral

Maximum 6 mg/kg daily.398


Adults


Hypertension

Oral

Maximum 450 mg daily.115


Dosage of captopril/hydrochlorothiazide fixed-combination generally should not exceed captopril 150 mg and hydrochlorothiazide 50 mg daily.102


CHF

Oral

Maximum dosage recommended by manufacturer and some experts is 450 mg daily.115 333 Other experts suggest maximum dosage of 50 mg 3 times daily.377


Special Populations


Renal Impairment


Manufacturers recommend initial dosage of <75 mg daily; increase dosage in small increments at 1- to 2-week intervals.115 After desired therapeutic effect has been attained, slowly reduce dosage to minimum effective level.115


Patients with Clcr 10–50 mL/minute: 75% of usual captopril dosage or administration of usual dose every 12–18 hours suggested by some clinicians.211


Clcr <10 mL/minute: 50% of usual dosage or administration of usual dose every 24 hours suggested by some clinicians.211


Patients undergoing hemodialysis may require supplemental dose after dialysis.211


Fixed-combination captopril/hydrochlorothiazide tablets usually are not recommended for patients with severe renal impairment.102


Geriatric Patients


Hypertension

Usual adult dosages generally have been used; dosages of 6.25–12.5 mg 1–4 times daily used occasionally.175


Volume-and/or Salt-Depleted Patients


Correct volume and/or salt depletion prior to initiation of therapy or initiate therapy under close medical supervision using lower initial dosage.115 116 148 153 (See Dosage: CHF, under Dosage and Administration.)


Cautions for Capoten


Contraindications



  • Known hypersensitivity (e.g. history of angioedema) to captopril or another ACE inhibitor.115 147 325 326 333



Warnings/Precautions


Warnings


Hematologic Effects

Possible neutropenia or agranulocytosis; risk of neutropenia appears to depend principally on degree of renal impairment and presence of collagen vascular disease (e.g., systemic lupus erythematosus, scleroderma).115


Use with caution and only after careful risk/benefit assessment in patients with collagen vascular disease or those taking drugs known to affect leukocytes or immune response.115


If used in patients with renal impairment, determine complete and differential leukocyte counts prior to initiation of therapy, at about 2-week intervals for the first 3 months of therapy, and periodically thereafter.115 Discontinue therapy if confirmed neutrophil count is <1000/mm3.115


Proteinuria

Proteinuria possible, particularly in patients with prior renal disease and/or those receiving relatively high dosages (>150 mg daily).115 Usually occurs by the 8th month of treatment1 3 46 and subsides or clears within 6 months whether or not therapy is continued;115 however, may persist in some patients.a


Hypotension

Possible excessive hypotension, particularly in volume- and/or salt-depleted patients (e.g., those treated with diuretics or undergoing dialysis, patients with severe CHF).1 5 17 23 25 31 66 85 115 116 148 154 156


Hypotension may occur in patients undergoing surgery or during anesthesia with agents that produce hypotension; recommended treatment is fluid volume expansion.115


Transient hypotension is not a contraindication to additional doses; may reinstate therapy cautiously after BP is stabilized (e.g., with volume expansion).115


To minimize potential for hypotension, consider recent antihypertensive therapy, extent of BP elevation, sodium intake, fluid status, and other clinical conditions.a (See Special Populations under Dosage and Administration.) Discontinue other antihypertensive therapy, if possible, 1 week before initiating captopril, except in patients with severe hypertension.115 a Withholding diuretic therapy and/or increasing sodium intake approximately 3–7 days prior to initiation of captopril may minimize potential for severe hypotension.115 116 148 153


Initiate therapy in patients with CHF under close medical supervision; monitor closely for first 2 weeks following initiation of captopril or any increase in captopril or diuretic dosage.115


Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when used during pregnancy.102 115 239 240 241 402 (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.402


Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.401 402


Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.402 Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.239


Hepatic Effects

Clinical syndrome that usually is manifested initially by cholestatic jaundice and may progress to fulminant hepatic necrosis (occasionally fatal) reported rarely with ACE inhibitors.102 115 370


If jaundice or marked elevation of liver enzymes occurs, discontinue drug and monitor patient.115


Sensitivity Reactions


Anaphylactoid reactions and/or angioedema possible; if associated with laryngeal edema, may be fatal.115 333 Immediate medical intervention (e.g., epinephrine) for involvement of tongue, glottis, or larynx.115 Intestinal angioedema possible; consider in differential diagnosis of patients who develop abdominal pain.115


Anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing LDL apheresis with dextran sulfate absorption115 275 276 277 or following initiation of hemodialysis that utilized high-flux membrane.102 115 242 243 244


Life-threatening anaphylactoid reactions reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom.102 155 278


Not recommended in patients with a history of angioedema associated with or unrelated to ACE inhibitors.a


General Precautions


Renal Effects

Transient increases in BUN and Scr possible, especially in patients with preexisting renal impairment, sodium depletion, or hypovolemia; patients with renovascular hypertension, particularly those with bilateral renal-artery stenosis or those with renal-artery stenosis in a solitary kidney;5 86 115 117 122 123 124 207 208 209 333 372 or patients with chronic or severe hypertension in whom the glomerular filtration rate may decrease transiently.1 115


Possible increases in BUN and Scr in patients with CHF;115 206 333 rapidity of onset and magnitude may depend in part on degree of sodium depletion.148 156 206 372


Closely monitor renal function following initiation of therapy in such patients.86 87 115 117 122 123 124 333 372 Some patients may require dosage reduction or discontinuance of ACE inhibitor or diuretic and/or adequate sodium repletion.115 156 206 207 209


Hyperkalemia

Possible hyperkalemia,5 7 38 69 70 85 115 122 125 126 162 163 164 177 especially in patients with impaired renal function, CHF, or diabetes mellitus and those receiving drugs that can increase serum potassium concentration (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes).38 85 115 125 126 148 162 163 164 333 372 (See Interactions.)


Monitor serum potassium concentration carefully in these patients.126 162 163


Cough

Persistent and nonproductive cough; resolves after drug discontinuance.102 115 333


Valvular Stenosis

Possible risk of decreased coronary perfusion in patients with aortic stenosis when treated with captopril.a 115


Use of Fixed Combinations

When used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.102


Specific Populations


Pregnancy

Category C (1st trimester); Category D (2nd and 3rd trimesters).115 (See Fetal/Neonatal Morbidity and Mortality under Cautions and see Boxed Warning.)


Lactation

Distributed into milk.115 Discontinue nursing or the drug.115


Pediatric Use

Safety and efficacy not established; however, captopril has been used in children.115 Manufacturer states that captopril should be used only when other measures for controlling BP have not been effective.115


Possible excessive, prolonged, and unpredictable decreases in BP and associated complications (e.g., oliguria, seizures) in infants.115


Renal Impairment

Systemic exposure to captopril may be increased.115 (See Special Populations under Pharmacokinetics.) Initial dosage adjustment recommended in patients with severe renal impairment.115 (See Renal Impairment under Dosage and Administration.)


Deterioration of renal function may occur.115 211 Possible increased risk of neutropenia/agranulocytosis,115 proteinuria,115 and hyperkalemia.115 (See Warnings and General Precautions under Cautions.)


Use of captopril/hydrochlorothiazide fixed combination usually is not recommended in patients with severe renal impairment.102


Blacks

BP reduction may be smaller in black patients compared with nonblack patients;115 139 177 178 179 180 181 351 however, no apparent population difference during combined therapy with ACE inhibitor and thiazide diuretic.179 193 194 217 218 219 316 Use in combination with a diuretic.179 193 194 217 218 219 316


Higher incidence of angioedema reported with ACE inhibitors in blacks compared with other races.102 115 325 326 327 351 379 380


Common Adverse Effects


Rash, pruritus, cough, dysgeusia, proteinuria, tachycardia, chest pain, palpitations.115


Interactions for Capoten


Specific Drugs and Laboratory Tests






















































Drug



Interaction



Comments



Adrenergic neuron blocking agents (guanethidine)



Possible increased hypotensive effect115



Use with caution115



Antacids



Decreased rate and extent of captopril absorption197 201



Clinical importance is uncertain197 201



Antidiabetic agents, oral



Possible hypoglycemia in diabetic patients101



Consider risk of hypoglycemia if used concomitantly101



Allopurinol



Pharmacokinetic interaction unlikely115



β-adrenergic blocking agents



Increased (but less than additive) hypotensive effect115



Cimetidine



Neuropathy reporteda



Further documentation of interaction necessarya



Digoxin



Possible increased serum digoxin concentrations in patients with CHF198 199 200



Monitor serum digoxin concentration;198 200 reduction of digoxin dosage not required upon initiation of captopril198



Diuretics



Possible additive hypotensive effectsa


Pharmacokinetic interaction with furosemide unlikely115



Adjust dosage carefullya (see Dosage under Dosage and Administration)



Diuretics, potassium-sparing (amiloride, spironolactone, triamterene)



Possible hyperkalemia, especially in patients with renal impairment162 329 331 335



Use cautiously and only if hypokalemia is documented; monitor serum potassium carefully;85 115 125 126 148 162 163 164 discontinue or reduce dosage of potassium-sparing diuretic as necessary85 126 148 162 163



Insulin



Possible hypoglycemia in diabetic patients101



Consider risk of hypoglycemia101



Lithium



Possible increased serum lithium concentrations, particularly in patients receiving concomitant diuretic therapy115



Use with caution; monitor serum lithium concentrations frequently115



NSAIAs



Possible decreased antihypertensive response to captopril;283 284 285 286 287 288 289 290 333 364 potential for acute reduction of renal function;285 291 possible attenuation of hemodynamic actions of ACE inhibitors in patients with CHF333 364



Monitor BP carefully and be alert for evidence of impaired renal function;285 if interaction is suspected, discontinue NSAIA or modify captopril dosage or use another hypotensive agent285 286



Potassium supplements or potassium-containing salt substitutes



Possible hyperkalemia, especially in patients with renal impairment162



Use cautiously and only if hypokalemia is documented; monitor serum potassium carefully;85 115 125 126 148 162 163 164 discontinue or reduce dosage of potassium supplement as necessary85 126 148 162 163



Probenecid



Possible increased blood concentrations of captopril and its metabolites203 204 205 213



Test for urine acetone



Possible false-positive results with sodium nitroprusside reagent54 115



Vasodilating agents (e.g., hydralazine, nitrates, prazosin)



Possible increased hypotensive effect115



If possible, discontinue vasodilating agent before starting captopril; if vasodilating agent is resumed during captopril therapy, administer with caution and possibly at a lower dosage115


Capoten Pharmacokinetics


Absorption


Bioavailability


Rapidly absorbed following oral administration in fasting individuals,19 20 84 115 with peak blood concentration attained in 1 hour.19 Approximately 60–75% of an oral dose is absorbed.19 20 84 115


Onset


Hypotensive effect may be apparent within 15 minutes5 6 16 23 and usually is maximal in 1–2 hours after a single oral dose.1 3 10 15 16 17 21 24 29 Several weeks of therapy may be required before full effect on BP is achieved.1 3 5 16 21 28


Duration


Duration of action generally is 2–6 hours but appears to increase with increasing doses.a


Food


Food may decrease absorption of captopril by up to 25–40%;1 3 115 191 195 196 197 202 effect may not be clinically important.191 192 195


Distribution


Extent


Appears to be rapidly distributed into most body tissues, except CNS.1 5


Crosses the placenta and is distributed into milk.115


Plasma Protein Binding


25–30%1 3 22 (mainly albumin).3


Elimination


Metabolism


About half the absorbed dose is rapidly metabolized.3 5 19 Captopril and its metabolites may undergo reversible interconversions.3


Elimination Route


Excreted in urine (95%) as unchanged drug (40–50%) and metabolites.3 19 20 22 115


Half-life


<2 hours.115


Special Populations


Elimination half-life is about 20–40 hours in patients with Clcr <20 mL/minute 3 and up to 6.5 days in anuric patients.5 22


Stability


Storage


Oral


Tablets

Tight containers at ≤30°C.115


Tablets (Captopril and Hydrochlorothiazide)

Tight containers at ≤30°C.102


ActionsActions



  • Suppresses the renin-angiotensin-aldosterone system.1



Advice to Patients



  • Risk of angioedema, anaphylactoid reactions, or other sensitivity reactions.115 Importance of reporting sensitivity reactions (e.g., edema of face, eyes, lips, tongue, or extremities; hoarseness; swallowing or breathing with difficulty) immediately to clinician and of discontinuing the drug.115




  • Importance of reporting signs of infection (e.g., sore throat, fever).115




  • Risk of hypotension.115 Importance of informing clinicians promptly if lightheadedness or fainting occurs.115




  • Importance of adequate fluid intake; risk of volume depletion with excessive perspiration, dehydration, vomiting, or diarrhea.115




  • Importance of not discontinuing or interrupting therapy unless instructed by a clinician.115




  • Risks of use during pregnancy.115 401 402 (See Boxed Warning.)




  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (including salt substitutes containing potassium) as well as any concomitant illnesses.115




  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.115




  • Importance of taking 1 hour before meals.115




  • Importance of advising patients of other important precautionary information.115 (See Cautions.)



Preparations


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.


* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name




























Captopril

Routes



Dosage Forms



Strengths



Brand Names



Manufacturer



Oral



Tablets



12.5 mg*



Capoten (scored)



Par



25 mg*



Capoten (scored)



Par



50 mg*



Capoten (scored)



Par



100 mg*



Capoten (scored)



Par


* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
















































Captopril and Hydrochlorothiazide

Routes



Dosage Forms



Strengths



Brand Names



Manufacturer



Oral



Tablets



25 mg Captopril and Hydrochlorothiazide 15 mg*



Capozide (scored)



Par



Captopril and Hydrochlorothiazide Tablets



Endo, Mylan, Sandoz, Teva



25 mg Captopril and Hydrochlorothiazide 25 mg*



Capozide (scored)



Par



Captopril and Hydrochlorothiazide Tablets



Endo, Mylan, Sandoz, Teva



50 mg Captopril and Hydrochlorothiazide 15 mg*



Capozide (scored)



Par



Captopril and Hydrochlorothiazide Tablets



Endo, Mylan, Sandoz, Teva



50 mg Captopril and Hydrochlorothiazide 25 mg*



Capozide (scored)



Par



Captopril and Hydrochlorothiazide Tablets



Endo, Mylan, Sandoz, Teva


Comparative Pricing


This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.


Capozide 50-25MG Tablets (PAR): 30/$95.99 or 90/$269.98


Captopril 100MG Tablets (WEST-WARD): 90/$19.99 or 180/$29.97


Captopril 12.5MG Tablets (WEST-WARD): 100/$12.99 or 200/$18.98


Captopril 25MG Tablets (TEVA PHARMACEUTICALS USA): 90/$13.99 or 180/$26.99


Captopril 50MG Tablets (WEST-WARD): 100/$16.99 or 200/$22.97


Captopril-Hydrochlorothiazide 25-15MG Tablets (MYLAN): 90/$47.99 or 270/$114.97


Captopril-Hydrochlorothiazide 25-25MG Tablets (MYLAN): 90/$44.99 or 270/$125.99


Captopril-Hydrochlorothiazide 50-15MG Tablets (TEVA PHARMACEUTICALS USA): 60/$53.99 or 180/$154.98


Captopril-Hydrochlorothiazide 50-25MG Tablets (MYLAN): 60/$53.99 or 180/$154.99



Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.


The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions April 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.


† Use is not currently included in the labeling approved by the US Food and Drug Administration.




References



1. ER Squibb & Sons, Inc. Capoten prescribing information. Princeton, NJ; 1981 Mar.



3. ER Squibb & Sons, Inc. Capoten (captopril) monograph. Princeton, NJ; 1981 Apr.



4. Atkinson AB, Robertson JIS. Captopril in the treatment of clinical hypertension and cardiac failure. Lancet. 1979; 2:836-9. [IDIS 102581] [PubMed 90928]



5. Heel RC, Brogden RN, Speight TM et al. Captopril: a preliminary review of its pharmacological properties and therapeutic efficacy. Drugs. 1980; 20:409-52. [IDIS 134943] [PubMed 7009133]



6. Ferguson RK, Turini GA, Brunner HR et al. A specific orally active inhibitor of angiotensin-converting enzyme in man. Lancet. 1977; 1:775-8. [IDIS 78256] [PubMed 66571]



7. Gavras H, Brunner HR, Turini GA et al. Antihypertensive effect of the oral angiotensin converting-enzyme inhibitor SQ 14225 in man. N Engl J Med. 1978; 298:991-5. [IDIS 80115] [PubMed 205788]



8. Larochelle P, Genest J, Kuchel O et al. Effect of captopril (SQ 14225) on blood pressure, plasma renin activity and angiotensin I converting enzyme activity. Can Med Assoc J. 1979; 121:309-16. [IDIS 100999] [PubMed 223756]



9. Swartz S, Williams GH, Hollenberg NK et al. Increase in prostaglandins during converting enzyme inhibition. Clin Sci. 1980; 59(Suppl):133-5S.



10. Brunner HR, Gavras H, Waeber B et al. Oral angiotensin-converting enzyme inhibitor in long-term treatment of hypertensive patients. Ann Intern Med. 1979; 90:19-23. [IDIS 96700] [PubMed 217289]



11. Johnston CI, Millar JA, McGrath BP et al. Long-term effects of captopril (SQ 14225) on blood-pressure and hormone levels in essential hypertension. Lancet. 1979; 2:493-6. [IDIS 103099] [PubMed 90216]



12. McCaa CS, Langford HG, Cushman WC et al. Response of arterial blood pressure, plasma renin activity and aldosterone concentration to long-term administration of captopril to patients with severe, treatment-resistant malignant hypertension. Clin Sci. 1979; 57(Suppl):371-3S.



13. Fagard R, Amery A, Reybrouck T et al. Acute and chronic systemic and pulmonary hemodynamic effects of angiotensin converting enzyme inhibition with captopril in hypertensive patients. Am J Cardiol. 1980; 46:295-300. [IDIS 122485] [PubMed 6250392]



14. Maruyama A, Ogihara T, Naka T et al. Long-term effects of captopril in hypertension. Clin Pharmacol Ther. 1980; 28:316-23. [IDIS 123828] [PubMed 6996895]



15. Mimran A, Brunner HR, Turini GA et al. Effect of captopril on renal vascular tone in patients with essential hypertension. Clin Sci. 1979; 57(Suppl):421-3S. [IDIS 109948] [PubMed 519950]



16. Case DB, Atlas SA, Laragh JH et al. Clinical experience with blockade of the renin-angiotensin-aldosterone system by an oral converting-enzyme inhibitor (SQ 14,225, captopril) in hypertensive patients. Prog Cardiovasc Dis. 1978; 21:195-206. [PubMed 214819]



17. Morganti A, Pickering TG, Lopez-Ovejero JA et al. Endocrine and cardiovascular influences of converting enzyme inhibition with SQ 14225 in hypertensive patients in the supine position and during head-up tilt before and after sodium depletion. J Clin Endocrinol Metab. 1980; 50:748-54. [IDIS 124889] [PubMed 6245101]



19. Kripalani KJ, McKinstry DN, Singhvi SM et al. Disposition of captopril in normal subjects. Clin Pharmacol Ther. 1980; 27:636-41. [IDIS 113124] [PubMed 6989546]



20. McKinstry DN, Kripalani KJ, Migdalof BH et al. The effect of repeated administration of captopril (CP) on its disposition in hypertensive patients. Clin Pharmacol Ther. 1980; 27:270-1.



21. Case DB, Atlas SA, Laragh JH et al. Use of

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