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==Lisinopril==
Lisinopril is an oral long-acting angiotensin converting enzyme inhibitor. Lisinopril, a synthetic peptide derivative, is chemically described as (S)-1-[N2-(1-carboxy-3-phenylpropyl)-L-lysyl]-L-proline dihydrate. Its empirical formula is C21H31N3O5.2H2O and its
structural formula is:

[[Image:Lisinopril.jpg‎|Lisinopril]]

===[[Lisinopril Boxed Warning|Boxed Warning]]===

===[[Lisinopril Mechanism of Action|Mechanism of Action]]===

===[[Lisinopril Indications and Usage|Indications and Usage]]===

===[[Lisinopril Dosage and Administration|Dosage and Administration]]===

===How Supplied===
:2.5 mg Tablets
:5 mg Tablets
:10 mg Tablets
:20 mg Tablets                        
:30 mg Tablets
:40 mg Tablets

===Contraindications===

Lisinopril is contraindicated in patients who are hypersensitive to this product and in patients with a history of angioedema related to previous treatment with an angiotensin converting enzyme inhibitor and in patients with hereditary or idiopathic angioedema. 

===Drug Interactions===

<b>Hypotension</b>

<i>Patients on Diuretic Therapy </i>

Patients on diuretics and especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with lisinopril. The possibility of hypotensive effects with lisinopril can be minimized by either discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with lisinopril. If it is necessary to continue the diuretic, initiate therapy with lisinopril at a dose of 5 mg daily, and provide close medical supervision after the initial dose until blood pressure has stabilized. When a diuretic is added to the therapy of a patient receiving lisinopril, an additional antihypertensive effect is usually observed. Studies with ACE inhibitors in combination with diuretics indicate that the dose of the ACE inhibitor can be reduced when it is given with a diuretic.

<i>Antidiabetics</i>

Epidemiological studies have suggested that concomitant administration of ACE inhibitors and antidiabetic medicines (insulins, oral hypoglycemic agents) may cause an increased blood-glucose-lowering effect with risk of hypoglycemia. This phenomenon appeared to be more likely to occur during the first weeks of combined treatment and in patients with renal impairment. In diabetic patients treated with oral antidiabetic agents or insulin, glycemic control should be closely monitored for hypoglycemia, especially during the first month of treatment with an ACE inhibitor. 

<i>Non-steroidal Anti-inflammatory Agents</i>

In some patients with compromised renal function who are being treated with non-steroidal anti-inflammatory drugs, the co¬administration of lisinopril may result in further deterioration of renal function. These effects are usually reversible. In a study in 36 patients with mild to moderate hypertension where the antihypertensive effects of lisinopril alone were compared to lisinopril given concomitantly with indomethacin, the use of indomethacin was associated with a reduced effect, although the difference between the two regimens was not significant. 

<i>Other Agents</i>

Lisinopril has been used concomitantly with nitrates and/or digoxin without evidence of clinically significant adverse interactions. 
This included post myocardial infarction patients who were receiving intravenous or transdermal nitroglycerin. No clinically important pharmacokinetic interactions occurred when lisinopril was used concomitantly with propranolol or hydrochlorothiazide. The presence of food in the stomach does not alter the bioavailability of lisinopril. 

<i>Agents Increasing Serum Potassium </i>

Lisinopril attenuates potassium loss caused by thiazide-type diuretics. Use of lisinopril with potassium-sparing diuretics (e.g., spironolactone, eplerenone, triamterene or amiloride), potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium. Therefore, if concomitant use of these agents is indicated because of demonstrated hypokalemia, they should be used with caution and with frequent monitoring of serum potassium. Potassium-sparing agents should generally not be used in patients with heart failure who are receiving lisinopril. 

<i>Lithium</i>

Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs which cause elimination of sodium, including ACE inhibitors. Lithium toxicity was usually reversible upon discontinuation of lithium and the ACE inhibitor. It is recommended that serum lithium levels be monitored frequently if lisinopril is administered concomitantly with lithium. 

<i>Gold</i>

Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including lisinopril. 

<i>Carcinogenesis, Mutagenesis, Impairment of Fertility</i>

There was no evidence of a tumorigenic effect when lisinopril was administered for 105 weeks to male and female rats at doses up to 90 mg/kg/day (about 56 or 9 times* the maximum recommended daily human dose, based on body weight and body surface area, respectively). There was no evidence of carcinogenicity when lisinopril was administered for 92 weeks to (male and female) mice at doses up to 135 mg/kg/day (about 84 times* the maximum recommended daily human dose). This dose was 6.8 times the maximum human dose based on body surface area in mice. 

:Calculations assume a human weight of 50 kg and human body surface area of 1.62 m2. 

Lisinopril was not mutagenic in the Ames microbial mutagen test with or without metabolic activation. It was also negative in a forward mutation assay using Chinese hamster lung cells. Lisinopril did not produce single strand DNA breaks in an in vitro alkaline elution rat hepatocyte assay. In addition, lisinopril did not produce increases in chromosomal aberrations in an in vitro test in Chinese hamster ovary cells or in an in vivo study in mouse bone marrow. 

There were no adverse effects on reproductive performance in male and female rats treated with up to 300 mg/kg/day of lisinopril. 

This dose is 188 times and 30 times the maximum human dose when based on mg/kg and mg/m2, respectively. 

<i>Pediatric Use</i>

Antihypertensive effects of lisinopril have been established in hypertensive pediatric patients aged 6 to 16 years. 
There are no data on the effect of lisinopril on blood pressure in pediatric patients under the age 6 or in pediatric patients with glomerular filtration rate <30 mL/min/1.73 m2.

<i>Geriatric Use </i>

Clinical studies of lisinopril in patients with hypertension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other clinical experience in this population 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. 

In the ATLAS trial of lisinopril in patients with congestive heart failure, 1,596 (50%) were 65 and over, while 437 (14%) were 75 and over. In a clinical study of lisinopril in patients with myocardial infarctions 4,413 (47%) were 65 and over, while 1,656 (18%) were 75 and over. In these studies, no overall differences in safety or effectiveness were observed between elderly and younger patients, and other reported clinical experiences has not identified differences in responses between the elderly and younger patients.

Other reported clinical experience has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. 

Pharmacokinetic studies indicate that maximum blood levels and area under the plasma concentration time curve (AUC) are doubled in older patients.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Evaluation of patients with hypertension, congestive heart failure, or myocardial infarction should always include assessment of renal function.

===Pregnancy===
Pregnancy Category C (first trimester) and D (second and third trimesters)

Nursing Mothers 
Milk of lactating rats contains radioactivity following administration of 14C lisinopril. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ACE inhibitors, a decision should be made whether to discontinue nursing or discontinue lisinopril, taking into account the importance of the drug to the mother. 

===Adverse Effects===
<b>Hypertension</b>

In clinical trials in patients with hypertension treated with lisinopril, discontinuation of therapy due to clinical adverse experiences occurred in 5.7% of patients. The overall frequency of adverse experiences could not be related to total daily dosage within the recommended therapeutic dosage range. 

For adverse experiences occurring in greater than 1% of patients with hypertension treated with lisinopril or lisinopril plus hydrochlorothiazide in controlled clinical trials, and more frequently with lisinopril and/or lisinopril plus hydrochlorothiazide than placebo, comparative incidence data data are listed in the table below:

[[Image:Adverse_Reactions_in_the_Treatment_of_Hypertension.JPG‎|Adverse Reactions in the Treatment of Hypertension]]

Chest and back pain were also seen but were more common on placebo then lisinopril.

<b>Heart Failure</b>

In patients with heart failure treated with lisinopril for up to four years, discontinuation of therapy due to clinical adverse experiences occurred in 11% of patients. In controlled studies in patients with heart failure, therapy was discontinued in 8.1% of patients treated with lisinopril for 12 weeks, compared to 7.7% of patients treated with placebo for 12 weeks. 
The following table lists those adverse experiences which occurred in greater than 1% of patients with heart failure treated with lisinopril or placebo for up to 12 weeks in controlled clinical trials, and more on lisinopril than placebo.

[[Image:Adverse_Reactions_in_the_Treatment_of_Heart_Failure.JPG|Adverse Reactions in the Treatment of Heart Failure]]

Also observed at > 1% with lisinopril but more frequent or as frequent on placebo than lisinopril in controlled trials were asthenia, angina pectoris, nausea, dyspnea, cough, and pruritus.

Worsening of heart failure, anorexia, increased salivation, muscle cramps, back pain, myalgia, depression, chest sound abnormalities, and pulmonary edema were also seen in controlled clinical trials, but were more common on placebo than lisinopril.
  
In the two-dose ATLAS trial in heart failure patients, withdrawals due to adverse events were not different between the low and high groups, either in total number of discontinuation (17 to 18%) or in rare specific events (<1%).  The following adverse events, mostly related to ACE inhibition, were reported more commonly in the high dose group:

[[Image:Adverse_Reactions_in_the_ATLAS_trial_of_Lisinopril.JPG|ATLAS Trial]]

<b>Acute Myocardial Infarction</b>

In the GISSI-3 trial, in patients treated with lisinopril for six weeks following acute myocardial infarction, discontinuation of therapy occurred in 17.6% of patients. 

Patients treated with lisinopril had a significantly higher incidence of hypotension and renal dysfunction compared with patients not taking lisinopril.

In the GISSI-3 trial, hypotension (9.7%), renal dysfunction (2%), cough (0.5%), post infarction angina (0.3%), skin rash and generalized edema (0.01%), and angioedema (0.01%) resulted in withdrawal of treatment. In elderly patients treated with lisinopril, discontinuation due to renal dysfunction was 4.2%. 

Other clinical adverse experiences occurring in 0.3% to 1% of patients with hypertension or heart failure treated with lisinopril in controlled clinical trials and rarer, serious, possibly drug-related events reported in uncontrolled studies or marketing experience are listed below, and within each category are in order of decreasing severity: 

<b>Body as a Whole</b>

Anaphylactoid reactions, syncope, orthostatic effects, chest discomfort, pain, pelvic pain, flank pain, edema, facial edema, virus infection, fever, chills, malaise. 

<b>Cardiovascular0</b>

Cardiac arrest; myocardial infarction or cerebrovascular accident possibly secondary to excessive hypotension in high risk patients; pulmonary embolism and infarction, arrhythmias (including ventricular tachycardia, atrial tachycardia, atrial fibrillation, bradycardia and premature ventricular contractions), palpitations, transient ischemic attacks, paroxysmal nocturnal dyspnea, orthostatic hypotension, decreased blood pressure, peripheral edema, vasculitis. 

<b>Digestive</b>

Pancreatitis, hepatitis (hepatocellular or cholestatic jaundice), vomiting, gastritis, dyspepsia, heartburn, gastrointestinal cramps, constipation, flatulence, dry mouth. 

<b>Hematologic</b>

Rare cases of bone marrow depression, hemolytic anemia, leukopenia/neutropenia and thrombocytopenia. 

<b>Endocrine</b>

Diabetes mellitus. 

<b>Metabolic</b>

Weight loss, dehydration, fluid overload, gout, weight gain. 
:Cases of hypoglycemia in diabetic patients on oral antidiabetic agents or insulin have been reported in post-marketing experience

<b>Musculoskeletal</b>

Arthritis, arthralgia, neck pain, hip pain, low back pain, joint pain, leg pain, knee pain, shoulder pain, arm pain, lumbago. 

<b>Nervous System/Psychiatric</b>

Stroke, ataxia, memory impairment, tremor, peripheral neuropathy (e.g., dysesthesia), spasm, paresthesia, confusion, insomnia, somnolence, hypersomnia, irritability and nervousness. 

<b>Respiratory System</b>

Malignant lung neoplasms, hemoptysis, pulmonary infiltrates, bronchospasm, asthma, pleural effusion, pneumonia, eosinophilic pneumonitis, bronchitis, wheezing, orthopnea, painful respiration, epistaxis, laryngitis, sinusitis, pharyngeal pain, pharyngitis, rhinitis, rhinorrhea. 

<b>Skin</b>

Urticaria, alopecia, herpes zoster, photosensitivity, skin lesions, skin infections, pemphigus, erythema, flushing, diaphoresis, cutaneous pseudolymphoma. Other severe skin reactions have been reported rarely, including toxic epidermal necrolysis and Stevens-Johnson syndrome; causal relationship has not been established. 

<b>Special Senses</b>

Visual loss, diplopia, blurred vision, tinnitus, photophobia, taste disturbances. 

<b>Urogenital System</b>

Acute renal failure, oliguria, anuria, uremia, progressive azotemia, renal dysfunction, pyelonephritis, dysuria, urinary tract infection, breast pain. 

<b>Miscellaneous</b>

A symptom complex has been reported which may include a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia, fever, vasculitis, eosinophilia and leukocytosis. Rash, photosensitivity or other dermatological manifestations may occur alone or in combination with these symptoms. 

<b>Angioedema</b>

Angioedema has been reported in patients receiving lisinopril (0.1%) with an incidence higher in Black than in non-Black patients. Angioedema associated with laryngeal edema may be fatal. If angioedema of the face, extremities, lips, tongue, glottis and/or larynx occurs, treatment with lisinopril should be discontinued and appropriate therapy instituted immediately.
In rare cases, intestinal angioedema has been reported in post marketing experience. 

<b>Hypotension</b>

In hypertensive patients, hypotension occurred in 1.2% and syncope occurred in 0.1% of patients with an incidence higher in Black than in non-Black patients. Hypotension or syncope was a cause of discontinuation of therapy in 0.5% of hypertensive patients. In patients with heart failure, hypotension occurred in 5.3% and syncope occurred in 1.8% of patients. These adverse experiences were possibly dose-related (see above data from ATLAS Trial) and caused discontinuation of therapy in 1.8% of these patients in the symptomatic trials. In patients treated with lisinopril for six weeks after acute myocardial infarction, hypotension (systolic blood pressure <100 mmHg) resulted in discontinuation of therapy in 9.7% of the patients.

<b>Cough</b>

<b>Pediatric Patients</b>

No relevant differences between the adverse experience profile for pediatric patients and that previously reported for adult patients were identified. 

===Clinical Laboratory Findings ===

<b>Serum Electrolytes:</b> Hyperkalemia, hyponatremia.

<b>Creatinine, Blood Urea Nitrogen:</b> Minor increases in blood urea nitrogen and serum creatinine, reversible upon discontinuation of therapy, were observed in about 2% of patients with essential hypertension treated with lisinopril alone. Increases were more common in patients receiving concomitant diuretics and in patients with renal artery stenosis. Reversible minor increases in blood urea nitrogen and serum creatinine were observed in approximately 11.6% of patients with heart failure on concomitant diuretic therapy. Frequently, these abnormalities resolved when the dosage of the diuretic was decreased. 

<b>Hemoglobin and Hematocrit:</b> Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.4 g% and 1.3 vol %, respectively) occurred frequently in patients treated with lisinopril but were rarely of clinical importance in patients without some other cause of anemia. In clinical trials, less than 0.1% of patients discontinued therapy due to anemia. Hemolytic anemia has been reported; a causal relationship to lisinopril cannot be excluded. 

<b>Liver Function Tests:</b> Rarely, elevations of liver enzymes and/or serum bilirubin have occurred.
In hypertensive patients, 2% discontinued therapy due to laboratory adverse experiences, principally elevations in blood urea nitrogen (0.6%), serum creatinine (0.5%) and serum potassium (0.4%). 

In the heart failure trials, 3.4% of patients discontinued therapy due to laboratory adverse experiences; 1.8% due to elevations in blood urea nitrogen and/or creatinine and 0.6% due to elevations in serum potassium. 

In the myocardial infarction trial, 2% of patients receiving lisinopril discontinued therapy due to renal dysfunction (increasing creatinine concentration to over 3 mg/dL or a doubling or more of the baseline serum creatinine concentration); less than 1% of patients discontinued therapy due to other laboratory adverse experiences: 0.1% with hyperkalemia and less than 0.1% with hepatic enzyme alterations. 

===Warnings===
<b>Anaphylactoid and Possibly Related Reactions</b>
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. 

<i>Head and Neck Angioedema </i>

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. ACE inhibitors have been associated with a higher rate of angioedema in Black than in non-Black patients. Lisinopril should be promptly discontinued and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms has occurred. Even in those instances where swelling of only the tongue is involved, without respiratory distress, patients may require prolonged observation since treatment with antihistamines and corticosteroids may not be sufficient. Very rarely, fatalities have been reported due to angioedema associated with laryngeal edema or tongue edema. Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. 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.

<i>Intestinal Angioedema</i>

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

<i>Anaphylactoid Reactions During Desensitization</i>

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. 

<i>Anaphylactoid Reactions During Membrane Exposure</i>

Sudden and potentially life-threatening anaphylactoid reactions have been reported in some patients dialyzed with high-flux
membranes (e.g., AN69¶) and treated concomitantly with an ACE inhibitor. In such patients, dialysis must be stopped immediately,
and aggressive therapy for anaphylactoid reactions must be initiated. Symptoms have not been relieved by antihistamines in these
situations. In these patients, consideration should be given to using a different type of dialysis membrane or a different class of
antihypertensive agent. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with
dextran sulfate absorption.

<b>Hypotension</b>

Excessive hypotension is rare in patients with uncomplicated hypertension treated with lisinopril alone.
Patients with heart failure given lisinopril commonly have some reduction in blood pressure, with peak blood pressure reduction
occurring 6 to 8 hours post dose. Evidence from the two-dose ATLAS trial suggested that incidence of hypotension may increase
with dose of lisinopril in heart failure patients. Discontinuation of therapy because of continuing symptomatic hypotension usually
is not necessary when dosing instructions are followed; caution should be observed when initiating therapy.

Patients at risk of 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 with systolic blood pressure below
100 mmHg, 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.

Patients with acute myocardial infarction in the GISSI-3 trial had a higher (9% versus 3.7%) incidence of persistent hypotension
(systolic blood pressure < 90 mmHg for more than 1 hour) when treated with lisinopril. Treatment with lisinopril must not be initiated
in acute myocardial infarction patients at risk of further serious hemodynamic deterioration after treatment with a vasodilator (e.g.,
systolic blood pressure of 100 mmHg or lower) or cardiogenic shock.

In patients at risk of 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 lisinopril and/or diuretic is increased. Similar
considerations may apply to patients with ischemic heart or cerebrovascular disease, or in patients with acute myocardial infarction, 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.

<b>Leukopenia/Neutropenia/Agranulocytosis</b>

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 lisinopril are insufficient to show that lisinopril does not cause agranulocytosis at similar
rates. Marketing experience has revealed rare cases of leukopenia/neutropenia and bone marrow depression in which a causal
relationship to lisinopril cannot be excluded. Periodic monitoring of white blood cell counts in patients with collagen vascular disease
and renal disease should be considered.

<b>Hepatic Failure</b>

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice or hepatitis 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. 

<b>Fetal/Neonatal Morbidity and Mortality</b>

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 retrospective 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 nonstress 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. Lisinopril, 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 lisinopril were seen in studies of pregnant rats, mice, and rabbits. On a mg/kg basis, the doses used were up to 625 times (in mice), 188 times (in rats), and 0.6 times (in rabbits) the maximum recommended human dose. Tests:</b> Rarely, elevations of liver enzymes and/or serum bilirubin have occurred.

===Precautions===
<b>General</b> 

<i>Aortic Stenosis/Hypertrophic Cardiomyopathy </i>

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

<i>Impaired Renal Function</i>

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 lisinopril has 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 lisinopril had 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. 

<b>Evaluation of patients with hypertension, heart failure, or myocardial infarction should always include assessment of renal function.</b>

<i>Hyperkalemia </i>

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. Hyperkalemia can cause serious, sometimes fatal, arrhythmias. Lisinopril should be used cautiously, if at all, with these agents and with frequent monitoring of serum potassium.

<i>Cough</i>

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. 

<i>Surgery/Anesthesia </i>

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.