Lisinopril/Hydrochlorothiazide: Difference between revisions

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|warnings====Lisinopril===
|warnings====Lisinopril===


====Anaphylactoid and Possibly Related Reactions====
* Presumably because [[angiotensin-converting enzyme inhibitors]] affect the metabolism of [[eicosanoids]] and polypeptides, including endogenous [[bradykinin]], patients receiving ACE inhibitors (including Lisinopril) may be subject to a variety of adverse reactions, some of them serious.
====Head and Neck Angioedema====
* [[Angioedema]] of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with angiotensin converting enzyme inhibitors, including Lisinopril. This may occur at any time during treatment. In such cases Lisinopril should be promptly discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms has occurred. In instances where swelling has been confined to the face and lips the condition has generally resolved without treatment, although antihistamines have been useful in relieving symptoms. Angioedema associated with [[laryngeal edema]] may be fatal. Where there is involvement of the tongue, glottis or larynx, likely to cause airway obstruction, appropriate therapy, e.g., subcutaneous epinephrine solution 1:1000 (0.3 mL to 0.5 mL) and/or measures necessary to ensure a patent airway, should be promptly provided.
====Intestinal Angioedema====
* [[Intestinal angioedema]] has been reported in patients treated with [[ACE inhibitors]]. These patients presented with [[abdominal pain]] (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and [[C-1 esterase]] levels were normal. The angioedema was diagnosed by procedures including [[abdominal CT scan]] or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.
====Anaphylactoid reactions during desensitization====
* Two patients undergoing desensitizing treatment with [[hymenoptera venom]] while receiving ACE inhibitors sustained life-threatening [[anaphylactoid reactions]]. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge.
====Anaphylactoid reactions during membrane exposure====
* Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing [[low-density lipoprotein]] apheresis with dextran sulfate absorption.
====Hypotension====
* Excessive hypotension is rare in uncomplicated hypertensive patients treated with Lisinopril alone. Patients with heart failure given Lisinopril commonly have some reduction in blood pressure, especially with the first dose, but discontinuation of therapy for continuing symptomatic hypotension usually is not necessary when dosing instructions are followed; caution should be observed when initiating therapy. Patients at risk for excessive hypotension, sometimes associated with [[oliguria]] and/or progressive [[azotemia]], and rarely with acute renal failure and/or death, include those 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. It may be advisable to eliminate the diuretic (except in patients with heart failure), reduce the diuretic dose or increase salt intake cautiously before initiating therapy with Lisinopril in patients at risk for excessive hypotension who are able to tolerate such adjustments. In patients at risk for excessive [[hypotension]], therapy should be started under very close medical supervision and such patients should be followed closely for the first two weeks of treatment and whenever the dose of enalapril and/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 a [[myocardial infarction]] or [[cerebrovascular accident]].
* If excessive [[hypotension]] occurs, the patient should be placed in the supine position and, if necessary, receive an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further doses of Lisinopril, which usually can be given without difficulty once the blood pressure has stabilized. If symptomatic hypotension develops, a dose reduction or discontinuation of Lisinopril or concomitant [[diuretic]] may be necessary.
====Neutropenia/Agranulocytosis====
* Another angiotensin converting enzyme inhibitor, captopril, has been shown to cause [[agranulocytosis]] and [[bone marrow depression]], rarely in uncomplicated patients but more frequently in patients with renal impairment especially if they also have a [[collagen vascular disease]]. Available data from clinical trials of enalapril are insufficient to show that enalapril does not cause agranulocytosis at similar rates. Marketing experience has revealed cases of [[neutropenia]] or [[agranulocytosis]] in which a causal relationship to enalapril cannot be excluded. Periodic monitoring of white blood cell counts in patients with collagen vascular disease and renal disease should be considered.
====Hepatic Failure====
* Rarely, ACE inhibitors have been associated with a syndrome that starts with [[cholestatic jaundice]] and progresses to [[fulminant hepatic necrosis]], and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop [[jaundice]] or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.
====Fetal/Neonatal Morbidity and Mortality====
* ACE inhibitors can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature. When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible.
* In a published restrospective epidemiological study, infants whose mothers had taken an ACE inhibitor during their first trimester of pregnancy appeared to have an increased risk of major [[congenital malformations]] compared with infants whose mothers had not undergone first trimester exposure to ACE inhibitor drugs. The number of cases of birth defects is small and the findings of this study have not yet been repeated.
* The use of ACE inhibitors during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal [[skull hypoplasia]], [[anuria]], reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; [[oligohydramnios]] in this setting has been associated with fetal limb contractures, craniofacial deformation, and [[hypoplastic lung development]]. [[Prematurity]], [[intrauterine growth retardation]], and [[patent ductus arteriosus]] have also been reported, although it is not clear whether these occurrences were due to the ACE-inhibitor exposure.
* These adverse effects do not appear to have resulted from intrauterine ACE-inhibitor exposure that has been limited to the first trimester. Mothers whose embryos and fetuses are exposed to ACE inhibitors only during the first trimester should be so informed. Nonetheless, when patients become pregnant, physicians should make every effort to discontinue the use of Lisinopril as soon as possible.
* Rarely (probably less often than once in every thousand pregnancies), no alternative to ACE inhibitors will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intraamniotic environment.
* If [[oligohydramnios]] is observed, Lisinopril should be discontinued unless it is considered lifesaving for the mother. [[Contraction stress testing]] ([[CST]]), a [[non-stress test]] ([[NST]]), or [[biophysical profiling]] ([[BPP]]) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.
* Infants with histories of in utero exposure to ACE inhibitors should be closely observed for hypotension, oliguria, and [[hyperkalemia]]. If [[oliguria]] occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or [[dialysis]] may be required as means of reversing hypotension and/or substituting for disordered renal function. Enalapril, which crosses the placenta, has been removed from [[neonatal circulation]] by [[peritoneal dialysis]] with some clinical benefit, and theoretically may be removed by [[exchange transfusion]], although there is no experience with the latter procedure.
* No teratogenic effects of enalapril were seen in studies of pregnant rats and rabbits. On a body surface area basis, the doses used were 57 times and 12 times, respectively, the maximum recommended human daily dose (MRHDD).
===Aortic Stenosis/Hypertrophic Cardiomyopathy===
As with all vasodilators, lisinopril should be given with caution to patients with
obstruction in the outflow tract of the left ventricle.
===Impaired Renal Function===
* As a consequence of inhibiting the renin-angiotensin-aldosterone system, 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 Lisinopril, may be associated
with oliguria and/or progressive azotemia and rarely with acute renal failure and/or death.
* In hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine may occur.
Experience with another angiotensin-converting enzyme inhibitor suggests that these increases are usually reversible upon discontinuation of
Lisinopril and/or diuretic therapy. In such patients, renal function should be monitored during the first few weeks of therapy.
Some patients with hypertension or heart failure with no apparent pre-existing renal vascular disease have developed increases in blood
urea nitrogen and serum creatinine, usually minor and transient, especially when Lisinoprilhas been given concomitantly with a diuretic. This
is more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of the diuretic and/or Lisinopril
may be required.
* Patients with acute myocardial infarction in the GISSI-3 trial treated with Lisinoprilhad a higher (2.4% versus 1.1%) incidence of renal
dysfunction in-hospital and at six weeks (increasing creatinine concentration to over 3 mg/dL or a doubling or more of the baseline serum
creatinine concentration). In acute myocardial infarction, treatment with Lisinopril should be initiated with caution in patients with evidence of
renal dysfunction, defined as serum creatinine concentration exceeding 2 mg/dL. If renal dysfunction develops during treatment with Lisinopril
(serum creatinine concentration exceeding 3 mg/dL or a doubling from the pre-treatment value) then the physician should consider withdrawal
of Lisinopril.
* Evaluation of patients with hypertension, heart failure, or myocardial infarction should always include assessment of renal function.
===Hyperkalemia===
* In clinical trials hyperkalemia (serum potassium greater than 5.7 mEq/L) occurred in approximately 2.2% of hypertensive
patients and 4.8% of patients with heart failure. In most cases these were isolated values which resolved despite continued therapy.
Hyperkalemia was a cause of discontinuation of therapy in approximately 0.1% of hypertensive patients, 0.6% of patients with heart failure
and 0.1% of patients with myocardial infarction. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes
mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes,
which should be used cautiously, if at all, with lisinopril.
===Cough===
* Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been
reported with all ACE inhibitors, almost always resolving after discontinuation of therapy. ACE inhibitor-induced cough should be
considered in the differential diagnosis of cough.
===Surgery/Anesthesia===
* In patients undergoing major surgery or during anesthesia with agents that produce hypotension, lisinopril may 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.
===Angioedema===
* Angioedema, including laryngeal edema, may occur at any time during treatment with angiotensin-converting enzyme
inhibitors, including lisinopril. Patients should be so advised and told to report immediately any signs or symptoms suggesting
angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing or breathing) and to take no more drug until they
have consulted with the prescribing physician.
===Symptomatic Hypotension===
* Patients should be cautioned to report lightheadedness especially during the first few days of therapy. If actual
syncope occurs, the patient should be told to discontinue the drug until they have consulted with the prescribing physician.
* All patients should be cautioned that excessive perspiration and dehydration may lead to an excessive fall in blood pressure because of
reduction in fluid volume. Other causes of volume depletion such as vomiting or diarrhea may also lead to a fall in blood pressure; patients
should be advised to consult with their physician.
===Hyperkalemia===
* Patients should be told not to use salt substitutes containing potassium without consulting their physician.
===Leukopenia/Neutropenia===
* Patients should be told to report promptly any indication of infection (e.g., sore throat, fever) which may be a
sign of leukopenia/neutropenia.
===Pregnancy===
* Female patients of childbearing age should be told about the consequences of second- and third-trimester exposure to ACE
inhibitors, and they should also be told that these consequences do not appear to have resulted from intrauterine ACE inhibitor exposure that
has been limited to the first trimester. These patients should be asked to report pregnancies to their physicians as soon as possible.


===Hydrochlorothiazide===
===Hydrochlorothiazide===

Revision as of 16:17, 25 April 2014

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

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2], Amr Marawan, M.D. [3]

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Black Box Warning

{{{blackBoxWarningTitle}}}
See full prescribing information for complete Boxed Warning.
Condition Name: (Content)

Overview

Lisinopril/Hydrochlorothiazide is an Angiontensin converting enzyme inhibitor, Thiazide diuretic that is FDA approved for the {{{indicationType}}} of hypotension. There is a Black Box Warning for this drug as shown here. Common adverse reactions include hypotension (1.2% to 10.8% ), syncope (5.1% to 7% ), hyperkalemia (2.2% to 6.4% ), dizziness (5.4% to 18.9% ), headache (4.4% to 5.7% ), renal function tests abnormal and cough (3.5% ).

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Hypertension
  • Initial dose (not initial therapy): lisinopril 10 mg/hydrochlorothiazide 12.5 mg PO gd or lisinopril 20 mg/hydrochlorothiazide 12.5 mg PO gd.
  • Hydrochlorothiazide dosage should not be adjusted for 2-3 weeks, allow time for titration before increasing hydrochlorothiazide dose. lisinopril is effective at doses of 10 - 80 mg, and hydrochlorothiazide is effective at doses of 12.5 - 50 mg.
  • Maintenance: MAX dose lisinopril 80 mg/hydrochlorothiazide 50 mg PO qd.

Off-Label Use and Dosage (Adult)

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Safety and effectiveness have not been established in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Contraindications

Lisinopril

Hydrochlorothiazide

  • Hydrochlorothiazide is contraindicated in anuria. It is also contraindicated in patients who have previously demonstrated hypersensitivity to hydrochlorothiazide or other sulfonamide-derived drugs.

Warnings

{{{blackBoxWarningTitle}}}
See full prescribing information for complete Boxed Warning.
Condition Name: (Content)

Lisinopril

Anaphylactoid and Possibly Related Reactions

Head and Neck Angioedema

  • Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with angiotensin converting enzyme inhibitors, including Lisinopril. This may occur at any time during treatment. In such cases Lisinopril should be promptly discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms has occurred. In instances where swelling has been confined to the face and lips the condition has generally resolved without treatment, although antihistamines have been useful in relieving symptoms. Angioedema associated with laryngeal edema may be fatal. Where there is involvement of the tongue, glottis or larynx, likely to cause airway obstruction, appropriate therapy, e.g., subcutaneous epinephrine solution 1:1000 (0.3 mL to 0.5 mL) and/or measures necessary to ensure a patent airway, should be promptly provided.

Intestinal Angioedema

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

Anaphylactoid reactions during desensitization

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

Anaphylactoid reactions during membrane exposure

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

Hypotension

  • Excessive hypotension is rare in uncomplicated hypertensive patients treated with Lisinopril alone. Patients with heart failure given Lisinopril commonly have some reduction in blood pressure, especially with the first dose, but discontinuation of therapy for continuing symptomatic hypotension usually is not necessary when dosing instructions are followed; caution should be observed when initiating therapy. Patients at risk for excessive hypotension, sometimes associated with oliguria and/or progressive azotemia, and rarely with acute renal failure and/or death, include those 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. It may be advisable to eliminate the diuretic (except in patients with heart failure), reduce the diuretic dose or increase salt intake cautiously before initiating therapy with Lisinopril in patients at risk for excessive hypotension who are able to tolerate such adjustments. In patients at risk for excessive hypotension, therapy should be started under very close medical supervision and such patients should be followed closely for the first two weeks of treatment and whenever the dose of enalapril and/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 a myocardial infarction or cerebrovascular accident.
  • If excessive hypotension occurs, the patient should be placed in the supine position and, if necessary, receive an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further doses of Lisinopril, which usually can be given without difficulty once the blood pressure has stabilized. If symptomatic hypotension develops, a dose reduction or discontinuation of Lisinopril or concomitant diuretic may be necessary.

Neutropenia/Agranulocytosis

  • Another angiotensin converting enzyme inhibitor, captopril, has been shown to cause agranulocytosis and bone marrow depression, rarely in uncomplicated patients but more frequently in patients with renal impairment especially if they also have a collagen vascular disease. Available data from clinical trials of enalapril are insufficient to show that enalapril does not cause agranulocytosis at similar rates. Marketing experience has revealed cases of neutropenia or agranulocytosis in which a causal relationship to enalapril cannot be excluded. Periodic monitoring of white blood cell counts in patients with collagen vascular disease and renal disease should be considered.

Hepatic Failure

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

Fetal/Neonatal Morbidity and Mortality

  • ACE inhibitors can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature. When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible.
  • In a published restrospective epidemiological study, infants whose mothers had taken an ACE inhibitor during their first trimester of pregnancy appeared to have an increased risk of major congenital malformations compared with infants whose mothers had not undergone first trimester exposure to ACE inhibitor drugs. The number of cases of birth defects is small and the findings of this study have not yet been repeated.
  • The use of ACE inhibitors during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development. Prematurity, intrauterine growth retardation, and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to the ACE-inhibitor exposure.
  • These adverse effects do not appear to have resulted from intrauterine ACE-inhibitor exposure that has been limited to the first trimester. Mothers whose embryos and fetuses are exposed to ACE inhibitors only during the first trimester should be so informed. Nonetheless, when patients become pregnant, physicians should make every effort to discontinue the use of Lisinopril as soon as possible.
  • Rarely (probably less often than once in every thousand pregnancies), no alternative to ACE inhibitors will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intraamniotic environment.
  • Infants with histories of in utero exposure to ACE inhibitors should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function. Enalapril, which crosses the placenta, has been removed from neonatal circulation by peritoneal dialysis with some clinical benefit, and theoretically may be removed by exchange transfusion, although there is no experience with the latter procedure.
  • No teratogenic effects of enalapril were seen in studies of pregnant rats and rabbits. On a body surface area basis, the doses used were 57 times and 12 times, respectively, the maximum recommended human daily dose (MRHDD).

Aortic Stenosis/Hypertrophic Cardiomyopathy

As with all vasodilators, lisinopril should be given with caution to patients with obstruction in the outflow tract of the left ventricle.

Impaired Renal Function

  • As a consequence of inhibiting the renin-angiotensin-aldosterone system, 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 Lisinopril, may be associated with oliguria and/or progressive azotemia and rarely with acute renal failure and/or death.

  • In hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine may occur.

Experience with another angiotensin-converting enzyme inhibitor suggests that these increases are usually reversible upon discontinuation of Lisinopril and/or diuretic therapy. In such patients, renal function should be monitored during the first few weeks of therapy. Some patients with hypertension or heart failure with no apparent pre-existing renal vascular disease have developed increases in blood urea nitrogen and serum creatinine, usually minor and transient, especially when Lisinoprilhas been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of the diuretic and/or Lisinopril may be required.

  • Patients with acute myocardial infarction in the GISSI-3 trial treated with Lisinoprilhad a higher (2.4% versus 1.1%) incidence of renal

dysfunction in-hospital and at six weeks (increasing creatinine concentration to over 3 mg/dL or a doubling or more of the baseline serum creatinine concentration). In acute myocardial infarction, treatment with Lisinopril should be initiated with caution in patients with evidence of renal dysfunction, defined as serum creatinine concentration exceeding 2 mg/dL. If renal dysfunction develops during treatment with Lisinopril (serum creatinine concentration exceeding 3 mg/dL or a doubling from the pre-treatment value) then the physician should consider withdrawal of Lisinopril.

  • Evaluation of patients with hypertension, heart failure, or myocardial infarction should always include assessment of renal function.

Hyperkalemia

  • In clinical trials hyperkalemia (serum potassium greater than 5.7 mEq/L) occurred in approximately 2.2% of hypertensive

patients and 4.8% of patients with heart failure. In most cases these were isolated values which resolved despite continued therapy. Hyperkalemia was a cause of discontinuation of therapy in approximately 0.1% of hypertensive patients, 0.6% of patients with heart failure and 0.1% of patients with myocardial infarction. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes, which should be used cautiously, if at all, with lisinopril.

Cough

  • Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been

reported with all ACE inhibitors, almost always resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.

Surgery/Anesthesia

  • In patients undergoing major surgery or during anesthesia with agents that produce hypotension, lisinopril may 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.

Angioedema

  • Angioedema, including laryngeal edema, may occur at any time during treatment with angiotensin-converting enzyme

inhibitors, including lisinopril. Patients should be so advised and told to report immediately any signs or symptoms suggesting angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing or breathing) and to take no more drug until they have consulted with the prescribing physician.

Symptomatic Hypotension

  • Patients should be cautioned to report lightheadedness especially during the first few days of therapy. If actual

syncope occurs, the patient should be told to discontinue the drug until they have consulted with the prescribing physician.

  • All patients should be cautioned that excessive perspiration and dehydration may lead to an excessive fall in blood pressure because of

reduction in fluid volume. Other causes of volume depletion such as vomiting or diarrhea may also lead to a fall in blood pressure; patients should be advised to consult with their physician.

Hyperkalemia

  • Patients should be told not to use salt substitutes containing potassium without consulting their physician.

Leukopenia/Neutropenia

  • Patients should be told to report promptly any indication of infection (e.g., sore throat, fever) which may be a

sign of leukopenia/neutropenia.

Pregnancy

  • Female patients of childbearing age should be told about the consequences of second- and third-trimester exposure to ACE

inhibitors, and they should also be told that these consequences do not appear to have resulted from intrauterine ACE inhibitor exposure that has been limited to the first trimester. These patients should be asked to report pregnancies to their physicians as soon as possible.

Hydrochlorothiazide

  • Thiazides should be used with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.
  • Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
  • Sensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma.
  • In general, lithium should not be given with diuretics

Adverse Reactions

Clinical Trials Experience

Lisinopril

X To be filled later X

Hydrochlorothiazide

General
Cardiovascular
  • Orthostatic hypotension (seen in 1.8% of fosinopril sodium and hydrochlorothiazide patients and 0.3% of placebo patients; no patients discontinued therapy due to orthostatic hypotension), edema, flushing, rhythm disturbance, syncope.
Dermatologic
Endocrine/Metabolic
  • Sexual dysfunction, change in libido, breast mass.
Gastrointestinal
Immunologic
Musculoskeletal
Neurologic/Psychiatric
Respiratory
Special Senses
Urogenital
  • Urinary tract infection, urinary frequency, dysuria.
Laboratory Test Abnormalities
  • Serum electrolytes, uric acid, glucose, magnesium, cholesterol, triglycerides, and calcium (see PRECAUTIONS). Neutropenia.
  • Antihypertensive monotherapy with fosinopril has been evaluated for safety in more than 1500 patients, of whom approximately 450 patients were treated for a year or more. The observed adverse events included events similar to those seen with fosinopril sodium and hydrochlorothiazide; in addition, the following others have also been reported with fosinopril:
Cardiovascular
Dermatologic
Endocrine/Metabolic
Gastrointestinal
Hematologic
  • Lymphadenopathy.
Musculoskeletal
Neurologic/Psychiatric
  • Memory disturbance, tremor, confusion, mood change, sleep disturbance.
Respiratory
  • Bronchospasm, laryngitis/hoarseness, epistaxis, and (in two patients) a symptom-complex of cough, bronchospasm, and eosinophilia.
Special Senses
  • Vision disturbance, taste disturbance, eye irritation.
Urogenital
  • Renal insufficiency.
Laboratory Test Abnormalities
  • Elevations (usually transient and minor) of BUN and creatinine have been observed, but these have not been more frequent than in parallel patients treated with placebo. The hemoglobin in fosinopril-treated patients generally decreases by an average of 0.1 g/dL, but this nonprogressive change has never been symptomatic. Leukopenia and eosinophilia have also been reported.
  • Serum levels of liver function tests (transaminases, LDH, alkaline phosphatase and serum bilirubin) have occasionally been found to be elevated, and these elevations have lead to discontinuation of therapy in 0.7% of patients. Other risk factors for liver dysfunction have often been present in these cases; in any event the elevations generally have resolved after discontinuation of therapy with fosinopril.

Other Adverse Events Reported with ACE Inhibitors Other adverse effects reported with ACE inhibitors include cardiac arrest; pancytopenia, hemolytic anemia; aplastic anemia; thrombocytopenia; bullous pemphigus, exfoliative dermatitis; and a syndrome that may include one or more of arthralgia/arthritis, vasculitis, serositis, myalgia, fever, rash or other dermopathy, positive ANA titer, leukocytosis, eosinophilia, and elevated ESR. Hydrochlorothiazide has now 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.

Cardiovascular
Gastrointestinal
Hematologic
Immunologic
Metabolic
Musculoskeletal
  • Muscle spasm.
Neurologic
  • Vertigo, lightheadedness, transient blurred vision, headache, paresthesia, xanthopsia, weakness, and restlessness.

Postmarketing Experience

There is limited information regarding Lisinopril/Hydrochlorothiazide Postmarketing Experience in the drug label.

Drug Interactions

Lisinopril

X To be filled later X

Hydrochlorothiazide

  • Thiazides may decrease arterial responsiveness to norepinephrine, but not enough to preclude effectiveness of the pressor agent for therapeutic use.
  • Thiazides may increase the responsiveness to tubocurarine.
  • The diuretic, natriuretic, and antihypertensive effects of thiazide diuretics may be reduced by concurrent administration of nonsteroidal anti-inflammatory agents; the effects (if any) of these agents on the antihypertensive effect of fosinopril sodium and hydrochlorothiazide have not been studied.
  • Cholestyramine and Colestipol Resins:Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43%, respectively.
  • Hydrochlorothiazide: Under the auspices of the National Toxicology Program, rats and mice received hydrochlorothiazide for two years at doses up to 100 (rats) and 600 (mice) mg/kg/day. On a body weight basis, these highest doses were about 2400 times (mice) or 400 times (rats) the fosinopril sodium and hydrochlorothiazide dose of 12.5 mg, given to a 50 kg subject. On a body surface area basis, these doses are 226 times (mice) and 82 times (rats) the fosinopril sodium and hydrochlorothiazide dose. These studies uncovered no evidence of carcinogenicity in rats or female mice, but there was equivocal evidence of hepatocarcinogenicity in male mice.
  • Hydrochlorothiazide was not genotoxic in in vitro assays using strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 of Salmonella typhimurium (Ames assay); in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations; or in in vivo assays using mouse germinal cell chromosomes; Chinese Hamster bone-marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Using concentrations of hydrochlorothiazide of 43 to 1300 mg/mL, positive test results were obtained in the in vitro CHO Sister Chromatid Exchange (clastogenicity) test and in the Mouse Lymphoma Cell (mutagenicity) assays. Using an unspecified concentration of hydrochlorothiazide, positive test results were also obtained in the Aspergillus nidulans nondisjunction assay.
  • No adverse effects upon fertility were seen when rats and mice received dietary hydrochlorothiazide prior to mating and throughout gestation at doses up to 4 (rats) and 100 (mice) mg/kg/day. These doses are from 3.2 (body surface area basis in rats) to 400 (weight basis in mice) times greater than the dose received by a 50 kg human receiving 12.5 mg a day.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Lisinopril/Hydrochlorothiazide in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Lisinopril/Hydrochlorothiazide in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Lisinopril/Hydrochlorothiazide during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Lisinopril/Hydrochlorothiazide in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Lisinopril/Hydrochlorothiazide in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Lisinopril/Hydrochlorothiazide in geriatric settings.

Gender

There is no FDA guidance on the use of Lisinopril/Hydrochlorothiazide with respect to specific gender populations.

Race

There is no FDA guidance on the use of Lisinopril/Hydrochlorothiazide with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Lisinopril/Hydrochlorothiazide in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Lisinopril/Hydrochlorothiazide in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Lisinopril/Hydrochlorothiazide in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Lisinopril/Hydrochlorothiazide in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Lisinopril/Hydrochlorothiazide Administration in the drug label.

Monitoring

There is limited information regarding Lisinopril/Hydrochlorothiazide Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Lisinopril/Hydrochlorothiazide and IV administrations.

Overdosage

There is limited information regarding Lisinopril/Hydrochlorothiazide overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Lisinopril/Hydrochlorothiazide Pharmacology in the drug label.

Mechanism of Action

X To be filled later X

  • 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 renin-aldosterone 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.

Structure

There is limited information regarding Lisinopril/Hydrochlorothiazide Structure in the drug label.

Pharmacodynamics

There is limited information regarding Lisinopril/Hydrochlorothiazide Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Lisinopril/Hydrochlorothiazide Pharmacokinetics in the drug label.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

X To be filled later X

Hydrochlorothiazide
  • Under the auspices of the National Toxicology Program, rats and mice received hydrochlorothiazide for two years at doses up to 100 (rats) and 600 (mice) mg/kg/day. On a body weight basis, these highest doses were about 2400 times (mice) or 400 times (rats) the fosinopril sodium and hydrochlorothiazide dose of 12.5 mg, given to a 50 kg subject. On a body surface area basis, these doses are 226 times (mice) and 82 times (rats) the fosinopril sodium and hydrochlorothiazide dose. These studies uncovered no evidence of carcinogenicity in rats or female mice, but there was equivocal evidence of hepatocarcinogenicity in male mice.
  • Hydrochlorothiazide was not genotoxic in in vitro assays using strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 of Salmonella typhimurium (Ames assay); in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations; or in in vivo assays using mouse germinal cell chromosomes; Chinese Hamster bone-marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Using concentrations of hydrochlorothiazide of 43 to 1300 mg/mL, positive test results were obtained in the in vitro CHO Sister Chromatid Exchange (clastogenicity) test and in the Mouse Lymphoma Cell (mutagenicity) assays. Using an unspecified concentration of hydrochlorothiazide, positive test results were also obtained in the Aspergillus nidulans nondisjunction assay.
  • No adverse effects upon fertility were seen when rats and mice received dietary hydrochlorothiazide prior to mating and throughout gestation at doses up to 4 (rats) and 100 (mice) mg/kg/day. These doses are from 3.2 (body surface area basis in rats) to 400 (weight basis in mice) times greater than the dose received by a 50 kg human receiving 12.5 mg a day.

Clinical Studies

There is limited information regarding Lisinopril/Hydrochlorothiazide Clinical Studies in the drug label.

How Supplied

There is limited information regarding Lisinopril/Hydrochlorothiazide How Supplied in the drug label.

Storage

There is limited information regarding Lisinopril/Hydrochlorothiazide Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Lisinopril/Hydrochlorothiazide Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Lisinopril/Hydrochlorothiazide interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Lisinopril/Hydrochlorothiazide Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Lisinopril/Hydrochlorothiazide Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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