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| __NOTOC__
| | #REDIRECT [[Captopril#Warnings]] |
| {{Captopril}}
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| {{CMG}}; {{AE}} {{AM}}
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| ==WARNINGS==
| | [[Category: Cardiovascular Drugs]] |
| | | [[Category: Drug]] |
| ====Anaphylactoid and Possibly Related Reactions====
| | [[Category:ACE inhibitors]] |
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| Presumably because [[angiotensin-converting enzyme inhibitor]]s affect the metabolism of [[eicosanoids]] and polypeptides, including endogenous [[bradykinin]], patients receiving [[ACE inhibitor]]s (including captopril) may be subject to a variety of adverse reactions, some of them serious.
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| Do not co-administer [[aliskiren]] with captopril in patients with [[diabetes]].
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| ====Head and Neck Angioedema====
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| [[Angioedema]] involving the extremities, face, lips, mucous membranes, tongue, [[glottis]] or [[larynx]] has been seen in patients treated with [[ACE inhibitor]]s, including captopril. If angioedema involves the tongue, [[glottis]] or [[larynx]], airway obstruction may occur and be fatal. Emergency therapy, including but not necessarily limited to, subcutaneous administration of a 1:1000 solution of [[epinephrine]] should be promptly instituted.
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| Swelling confined to the face, mucous membranes of the mouth, lips and extremities has usually resolved with discontinuation of captopril; some cases required medical therapy.
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| ====Intestinal Angioedema====
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| [[Intestinal angioedema]] has been reported in patients treated with [[ACE inhibitors]]. These patients presented with [[abdominal pain]] (with or without [[nausea]] or [[vomiting]]); in some cases there was no prior history of facial [[angioedema]] and C1 esterase levels were normal. The [[angioedema]] was diagnosed by procedures including abdominal [[CT scan]] or [[ultrasound]], or at surgery, and symptoms resolved after stopping the [[ACE inhibitor]]. Intestinal [[angioedema]] should be included in the differential diagnosis of patients on [[ACE inhibitor]]s presenting with [[abdominal pain]]. | |
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| ====Anaphylactoid Reactions During Desensitization====
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| Two patients undergoing desensitizing treatment with [[hymenoptera venom]] while receiving [[ACE inhibitors]] sustained life-threatening [[anaphylactoid reactions]]. In the same patients, these reactions were avoided when [[ACE inhibitors]] were temporarily withheld, but they reappeared upon inadvertent rechallenge.
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| ====Anaphylactoid Reactions During Membrane Exposure====
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| [[Anaphylactoid reactions]] have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an [[ACE inhibitor]]. [[Anaphylactoid reactions]] have also been reported in patients undergoing [[low-density lipoprotein]] [[apheresis]] with dextran sulfate absorption.
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| ====Neutropenia/Agranulocytosis====
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| [[Neutropenia]] (<1000/mm<sup>3</sup>) with myeloid hypoplasia has resulted from use of captopril. About half of the [[neutropenic]] patients developed systemic or oral cavity infections or other features of the syndrome of [[agranulocytosis]].
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| The risk of [[neutropenia]] is dependent on the clinical status of the patient:
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| In clinical trials in patients with [[hypertension]] who have normal renal function (serum [[creatinine]] less than 1.6 mg/dL and no collagen vascular disease), [[neutropenia]] has been seen in one patient out of over 8,600 exposed.
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| In patients with some degree of [[renal failure]] (serum [[creatinine]] at least 1.6 mg/dL) but no [[collagen vascular disease]], the risk of [[neutropenia]] in clinical trials was about 1 per 500, a frequency over 15 times that for uncomplicated hypertension. Daily doses of captopril were relatively high in these patients, particularly in view of their [[diminished renal function]]. In foreign marketing experience in patients with [[renal failure]], use of [[allopurinol]] concomitantly with captopril has been associated with [[neutropenia]] but this association has not appeared in U.S. reports.
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| In patients with [[collagen vascular diseases]] (e.g., [[systemic lupus erythematosus]], [[scleroderma]]) and [[impaired renal function]], [[neutropenia]] occurred in 3.7 percent of patients in clinical trials.
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| While none of the over 750 patients in formal clinical trials of [[heart failure]] developed [[neutropenia]], it has occurred during the subsequent clinical experience. About half of the reported cases had serum [[creatinine]] ≥1.6 mg/dL and more than 75 percent were in patients also receiving [[procainamide]]. In [[heart failure]], it appears that the same risk factors for [[neutropenia]] are present.
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| The [[neutropenia]] has usually been detected within three months after captopril was started. [[Bone marrow]] examinations in patients with [[neutropenia]] consistently showed myeloid hypoplasia, frequently accompanied by erythroid hypoplasia and decreased numbers of [[megakaryocytes]] (e.g., hypoplastic bone marrow and [[pancytopenia]]); [[anemia]] and [[thrombocytopenia]] were sometimes seen.
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| In general, [[neutrophils]] returned to normal in about two weeks after captopril was discontinued, and serious infections were limited to clinically complex patients. About 13 percent of the cases of [[neutropenia]] have ended fatally, but almost all fatalities were in patients with serious illness, having [[collagen vascular disease]], [[renal failure]], [[heart failure]] or [[immunosuppressant therapy]], or a combination of these complicating factors.
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| Evaluation of the [[hypertensive]] or [[heart failure]] patient should always include assessment of renal function.
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| If captopril is used in patients with [[impaired renal function]], [[white blood cell]] and differential counts should be evaluated prior to starting treatment and at approximately two-week intervals for about three months, then periodically.
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| In patients with [[collagen vascular disease]] or who are exposed to other drugs known to affect the [[white cell]]s or immune response, particularly when there is [[impaired renal function]], captopril should be used only after an assessment of benefit and risk, and then with caution.
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| All patients treated with captopril should be told to report any signs of infection (e.g., [[sore throat]], [[fever]]). If [[infection]] is suspected, white cell counts should be performed without delay.
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| Since discontinuation of captopril and other drugs has generally led to prompt return of the white count to normal, upon confirmation of [[neutropenia]] ([[neutrophil]] count <1000/mm<sup>3</sup>) the physician should withdraw captopril and closely follow the patient's course.
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| ====Proteinuria====
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| Total urinary proteins greater than 1 g per day were seen in about 0.7 percent of patients receiving captopril. About 90 percent of affected patients had evidence of prior renal disease or received relatively high doses of captopril (in excess of 150 mg/day), or both. The [[nephrotic syndrome]] occurred in about one-fifth of [[proteinuric]] patients. In most cases, [[proteinuria]] subsided or cleared within six months whether or not captopril was continued. Parameters of renal function, such as [[BUN]] and [[creatinine]], were seldom altered in the patients with [[proteinuria]].
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| ====Hypotension====
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| Excessive [[hypotension]] was rarely seen in [[hypertensive]] patients but is a possible consequence of captopril use in salt/volume depleted persons (such as those treated vigorously with [[diuretics]]), patients with [[heart failure]] or those patients undergoing renal [[dialysis]]. (See PRECAUTIONS, Drug Interactions.)
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| In [[heart failure]], where the [[blood pressure]] was either normal or low, transient decreases in mean [[blood pressure]] greater than 20 percent were recorded in about half of the patients. This transient [[hypotension]] is more likely to occur after any of the first several doses and is usually well tolerated, producing either no symptoms or brief mild [[lightheadedness]], although in rare instances it has been associated with [[arrhythmia]] or conduction defects. Hypotension was the reason for discontinuation of drug in 3.6 percent of patients with [[heart failure]].
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| BECAUSE OF THE POTENTIAL FALL IN BLOOD PRESSURE IN THESE PATIENTS, THERAPY SHOULD BE STARTED UNDER VERY CLOSE MEDICAL SUPERVISION. A starting dose of 6.25 or 12.5 mg t.i.d. may minimize the [[hypotensive]] effect. Patients should be followed closely for the first two weeks of treatment and whenever the dose of captopril and/or [[diuretic]] is increased. In patients with [[heart failure]], reducing the dose of [[diuretic]], if feasible, may minimize the fall in [[blood pressure]].
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| [[Hypotension]] is not per se a reason to discontinue captopril. Some decrease of systemic [[blood pressure]] is a common and desirable observation upon initiation of captopril tablets, USP treatment in [[heart failure]]. The magnitude of the decrease is greatest early in the course of treatment; this effect stabilizes within a week or two, and generally returns to pretreatment levels, without a decrease in therapeutic efficacy, within two months.
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| ====Fetal Toxicity====
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| ======{{pcat}} D======
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| 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 captopril 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 mothers and fetus.
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| 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, captopril unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that [[oligohydramnios]] may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to captopril for [[hypotension]], [[oliguria]], and [[hyperkalemia]].
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| When captopril was given to rabbits at doses about 0.8 to 70 times (on a mg/kg basis) the maximum recommended human dose, low incidences of [[craniofacial malformations]] were seen. No teratogenic effects of captopril were seen in studies of pregnant rats and hamsters. On a mg/kg basis, the doses used were up to 150 times (in hamsters) and 625 times (in rats) the maximum recommended human dose.
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| ====Hepatic Failure====
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| Rarely, ACE inhibitors have been associated with a syndrome that starts with [[cholestatic jaundice]] and progresses to [[fulminant hepatic necrosis]] and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop [[jaundice]] or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.
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| ==PRECAUTIONS==
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| ====General====
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| ====Impaired Renal Function====
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| ====Hypertension====
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| Some patients with renal disease, particularly those with severe [[renal artery stenosis]], have developed increases in BUN and serum creatinine after reduction of blood pressure with captopril. Captopril dosage reduction and/or discontinuation of diuretic may be required. For some of these patients, it may not be possible to normalize blood pressure and maintain adequate renal perfusion.
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| ====Heart Failure====
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| About 20 percent of patients develop stable elevations of BUN and serum creatinine greater than 20 percent above normal or baseline upon long-term treatment with captopril. Less than 5 percent of patients, generally those with severe preexisting renal disease, required discontinuation of treatment due to progressively increasing creatinine; subsequent improvement probably depends upon the severity of the underlying renal disease.
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| ====Hyperkalemia====
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| Elevations in serum potassium have been observed in some patients treated with ACE inhibitors, including captopril. When treated with ACE inhibitors, patients at risk for the development of [[hyperkalemia]] include those with: [[renal insufficiency]]; [[diabetes mellitus]]; and those using concomitant [[potassium-sparing diuretics]], potassium supplements or potassium-containing salt substitutes; or other drugs associated with increases in serum potassium in a trial of type I diabetic patients with proteinuria, the incidence of withdrawal of treatment with captopril for hyperkalemia was 2% (4/207). in two trials of normotensive type I diabetic patients with microalbuminuria, no captopril group subjects had hyperkalemia (0/116). (See PRECAUTIONS: Information for Patients and Drug Interactions; ADVERSE REACTIONS: Altered Laboratory Findings.)
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| ====Cough====
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| Presumably due to the inhibition of the degradation of endogenous [[bradykinin]], persistent nonproductive cough has been reported with all ACE inhibitors, always resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.
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| ====Valvular Stenosis====
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| There is concern, on theoretical grounds, that patients with [[aortic stenosis]] might be at particular risk of decreased coronary perfusion when treated with vasodilators because they do not develop as much afterload reduction as others.
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| ====Surgery/Anesthesia====
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| In patients undergoing major surgery or during anesthesia with agents that produce hypotension, captopril will block [[angiotensin II]] formation secondary to compensatory [[renin]] release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.
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| ====Hemodialysis====
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| Recent clinical observations have shown an association of hypersensitivity-like (anaphylactoid) reactions during [[hemodialysis]] with high-flux dialysis membranes (e.g., AN69) in patients receiving ACE inhibitors. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of medication.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = CAPTOPRIL (CAPTOPRIL ) TABLET CAPTOPRIL TABLET [APOTEX CORP.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=2c0f1ee3-b2b7-a1bc-059a-d65bea6cd0ef | publisher = | date = | accessdate =}}</ref>
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| ==References==
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| {{Reflist}}
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| {{FDA}}
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| [[Category:Cardiovascular Drugs]]
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| [[Category:Drugs]]
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