Enalapril (Vasotec)
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Enalapril (Vasotec)

VASOTEC®
(enalapril)

WARNING

FETAL TOXICITY

See full prescribing information for complete boxed warning.

  • When pregnancy is detected, discontinue Vasotec® as soon as possible.
  • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. See WARNINGS: Fetal Toxicity

DRUG DESCRIPTION

VASOTEC® (enalapril maleate) is the maleate salt of enalapril, the ethyl ester of a long-acting angiotensin converting enzyme inhibitor, enalaprilat. Enalapril maleate is chemically described as (S)-1-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-L-proline, (Z)-2-butenedioate salt (1:1). Its empirical formula is C20H28N2O5•C4H4O4, and its structural formula is:

VASOTEC® (Enalapril) Structural Formula Illustration

Enalapril maleate is a white to off-white, crystalline powder with a molecular weight of 492.53. It is sparingly soluble in water, soluble in ethanol, and freely soluble in methanol.

Enalapril is a pro-drug; following oral administration, it is bioactivated by hydrolysis of the ethyl ester to enalaprilat, which is the active angiotensin converting enzyme inhibitor.

Enalapril maleate is supplied as 2.5 mg, 5 mg, 10 mg, and 20 mg tablets for oral administration. In addition to the active ingredient enalapril maleate, each tablet contains the following inactive ingredients: lactose, magnesium stearate, sodium bicarbonate, and starch. The 10 mg and 20 mg tablets also contain iron oxides.

What are the possible side effects of enalapril (Vasotec)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; severe stomach pain; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • feeling light-headed, fainting;
  • urinating more or less than usual, or not at all;
  • fever, chills, body aches, flu symptoms;
  • pale skin, easy bruising or bleeding;
  • fast, pounding, or uneven heartbeats;
  • chest pain; or
  • swelling, rapid weight gain.

Less serious side...

Read All Potential Side Effects and See Pictures of Vasotec »

What are the precautions when taking enalapril (Vasotec)?

Before taking enalapril, tell your doctor or pharmacist if you are allergic to it; or to other ACE inhibitors (such as benazepril); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: history of an allergic reaction which included swelling of the face/lips/tongue/throat (angioedema), blood filtering procedures (such as LDL apheresis, dialysis), high level of potassium in the blood, collagen vascular disease (such as lupus, scleroderma).

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are...

Read All Potential Precautions of Vasotec »

Last reviewed on RxList: 9/24/2012
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Hypertension

VASOTEC is indicated for the treatment of hypertension. VASOTEC is effective alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. The blood pressure lowering effects of VASOTEC and thiazides are approximately additive.

Heart Failure

VASOTEC is indicated for the treatment of symptomatic congestive heart failure, usually in combination with diuretics and digitalis. In these patients VASOTEC improves symptoms, increases survival, and decreases the frequency of hospitalization (see CLINICAL PHARMACOLOGY, Heart Failure, Mortality Trials for details and limitations of survival trials).

Asymptomatic Left Ventricular Dysfunction

In clinically stable asymptomatic patients with left ventricular dysfunction (ejection fraction ≤ 35 percent), VASOTEC decreases the rate of development of overt heart failure and decreases the incidence of hospitalization for heart failure (see CLINICAL PHARMACOLOGY, Heart Failure, Mortality Trials for details and limitations of survival trials).

In using VASOTEC consideration should be given to the fact that another angiotensin converting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen vascular disease, and that available data are insufficient to show that VASOTEC does not have a similar risk (see WARNINGS).

In considering use of VASOTEC, it should be noted that in controlled clinical trials ACE inhibitors have an effect on blood pressure that is less in black patients than in non-blacks. In addition, it should be noted that black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to non-blacks (see WARNINGS, Head and Neck Angioedema).

DOSAGE AND ADMINISTRATION

Hypertension

In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally may occur following the initial dose of VASOTEC. The diuretic should, if possible, be discontinued for two to three days before beginning therapy with VASOTEC to reduce the likelihood of hypotension (see WARNINGS). If the patient's blood pressure is not controlled with VASOTEC alone, diuretic therapy may be resumed.

If the diuretic cannot be discontinued an initial dose of 2.5 mg should be used under medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour (see WARNINGS and PRECAUTIONS: DRUG INTERACTIONS).

The recommended initial dose in patients not on diuretics is 5 mg once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range is 10 to 40 mg per day administered in a single dose or two divided doses. In some patients treated once daily, the antihypertensive effect may diminish toward the end of the dosing interval. In such patients, an increase in dosage or twice daily administration should be considered. If blood pressure is not controlled with VASOTEC alone, a diuretic may be added. Concomitant administration of VASOTEC with potassium supplements, potassium salt substitutes, or potassium-sparing diuretics may lead to increases of serum potassium (see PRECAUTIONS).

Dosage Adjustment in Hypertensive Patients with Renal Impairment

The usual dose of enalapril is recommended for patients with a creatinine clearance > 30 mL/min (serum creatinine of up to approximately 3 mg/dL). For patients with creatinine clearance ≤ 30 mL/min (serum creatinine ≥ 3 mg/dL), the first dose is 2.5 mg once daily. The dosage may be titrated upward until blood pressure is controlled or to a maximum of 40 mg daily.

Renal Status Creatinine-Clearance mL/min Initial Dose mg/day
Normal Renal Function > 80 mL/min 5 mg
Mild Impairment ≤ 80 > 30 mL/min 5 mg
Moderate to Severe Impairment ≤ 30 mL/min 2.5 mg
Dialysis Patients*
2.5 mg on dialysis days†
*See WARNINGS, Anaphylactoid reactions during membrane exposure
†Dosage on nondialysis days should be adjusted depending on the blood pressure response.

Heart Failure

VASOTEC is indicated for the treatment of symptomatic heart failure, usually in combination with diuretics and digitalis. In the placebo-controlled studies that demonstrated improved survival, patients were titrated as tolerated up to 40 mg, administered in two divided doses.

The recommended initial dose is 2.5 mg. The recommended dosing range is 2.5 to 20 mg given twice a day. Doses should be titrated upward, as tolerated, over a period of a few days or weeks. The maximum daily dose administered in clinical trials was 40 mg in divided doses.

After the initial dose of VASOTEC, the patient should be observed under medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour (see WARNINGS and PRECAUTIONS: DRUG INTERACTIONS). If possible, the dose of any concomitant diuretic should be reduced which may diminish the likelihood of hypotension. The appearance of hypotension after the initial dose of VASOTEC does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension.

Asymptomatic Left Ventricular Dysfunction

In the trial that demonstrated efficacy, patients were started on 2.5 mg twice daily and were titrated as tolerated to the targeted daily dose of 20 mg (in divided doses).

After the initial dose of VASOTEC, the patient should be observed under medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour (see WARNINGS and PRECAUTIONS: DRUG INTERACTIONS). If possible, the dose of any concomitant diuretic should be reduced which may diminish the likelihood of hypotension. The appearance of hypotension after the initial dose of VASOTEC does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension.

Dosage Adjustment in Patients with Heart Failure and Renal Impairment or Hyponatremia

In patients with heart failure who have hyponatremia (serum sodium less than 130 mEq/L) or with serum creatinine greater than 1.6 mg/dL, therapy should be initiated at 2.5 mg daily under close medical supervision (see DOSAGE AND ADMINISTRATION, Heart Failure, WARNINGS and PRECAUTIONS: DRUG INTERACTIONS). The dose may be increased to 2.5 mg b.i.d., then 5 mg b.i.d. and higher as needed, usually at intervals of four days or more if at the time of dosage adjustment there is not excessive hypotension or significant deterioration of renal function. The maximum daily dose is 40 mg.

Pediatric Hypertensive Patients

The usual recommended starting dose is 0.08 mg/kg (up to 5 mg) once daily. Dosage should be adjusted according to blood pressure response. Doses above 0.58 mg/kg (or in excess of 40 mg) have not been studied in pediatric patients (see CLINICAL PHARMACOLOGY, CLINICAL PHARMACOLOGY in Pediatric Patients).

VASOTEC is not recommended in neonates and in pediatric patients with glomerular filtration rate < 30 mL/min/1.73 m2, as no data are available.

Preparation of Suspension (for 200 mL of a 1.0 mg/mL suspension)

Add 50 mL of Bicitra® to a polyethylene terephthalate (PET) bottle containing ten 20 mg tablets of VASOTEC and shake for at least 2 minutes. Let concentrate stand for 60 minutes. Following the 60-minute hold time, shake the concentrate for an additional minute. Add 150 mL of Ora-Sweet SF™ to the concentrate in the PET bottle and shake the suspension to disperse the ingredients. The suspension should be refrigerated at 2-8°C (36-46°F) and can be stored for up to 30 days. Shake the suspension before each use.

HOW SUPPLIED

VASOTEC Tablets, 2.5 mg, are white, oval shaped tablet imprinted with “VASO 2.5” and scored on one side and scored on the other.

They are supplied as follows:

NDC 0187-0140-30 bottles of 30 (with desiccant)
NDC 0187-0140-90 unit of use bottles of 90 (with desiccant)

VASOTEC Tablets, 5 mg, are white, rounded triangle shaped tablet imprinted with “VASO 5” on one side and scored on the other.

They are supplied as follows:

NDC 0187-0141-30 bottles of 30 (with desiccant)
NDC 0187-0141-90 unit of use bottles of 90 (with desiccant)
NDC 0187-0141-10 bottles of 1,000 (with desiccant)

VASOTEC Tablets, 10 mg, are rust red, rounded triangle shaped tablet imprinted with “VASO 10” on one side and scored on the other.

They are supplied as follows:

NDC 0187-0142-30 bottles of 30 (with desiccant)
NDC 0187-0142-90 unit of use bottles of 90 (with desiccant)
NDC 0187-0142-10 bottles of 1,000 (with desiccant)

VASOTEC Tablets, 20 mg, are peach, rounded triangle shaped tablet imprinted with “VASO 20” on one side and scored on the other.

They are supplied as follows:

NDC 0187-0143-30 bottles of 30 (with desiccant)
NDC 0187-0143-90 unit of use bottles of 90 (with desiccant)
NDC 0187-0143-10 bottles of 1,000 (with desiccant)

Storage

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Keep container tightly closed. Protect from moisture. Dispense in a tight container as per USP, if product package is subdivided.

Manufactured in Canada by: Valeant Pharmaceuticals International, Inc. Steinbach, MB R5G 1Z7 Canada. For: Valeant Pharmaceuticals North America LLC Bridgewater, NJ 08807 USA.

Last reviewed on RxList: 9/24/2012
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

VASOTEC has been evaluated for safety in more than 10,000 patients, including over 1000 patients treated for one year or more. VASOTEC has been found to be generally well tolerated in controlled clinical trials involving 2987 patients. For the most part, adverse experiences were mild and transient in nature. In clinical trials, discontinuation of therapy due to clinical adverse experiences was required in 3.3 percent of patients with hypertension and in 5.7 percent of patients with heart failure. The frequency of adverse experiences was not related to total daily dosage within the usual dosage ranges. In patients with hypertension the overall percentage of patients treated with VASOTEC reporting adverse experiences was comparable to placebo.

Hypertension

Adverse experiences occurring in greater than one percent of patients with hypertension treated with VASOTEC in controlled clinical trials are shown below. In patients treated with VASOTEC, the maximum duration of therapy was three years; in placebo treated patients the maximum duration of therapy was 12 weeks.

  VASOTEC
(n=2314) Incidence (discontinuation)
Placebo
(n=230) Incidence
Body As A Whole
  Fatigue 3.0 ( < 0.1) 2.6
  Orthostatic Effects 1.2 ( < 0.1) 0
  Asthenia 1.1 (0.1) 0.9
Digestive
  Diarrhea 1.4 ( < 0.1) 1.7
  Nausea 1.4 (0.2) 1.7
Nervous/Psychiatric
  Headache 5.2 (0.3) 9.1
  Dizziness 4.3 (0.4) 4.3
Respiratory
  Cough 1.3 (0.1) 0.9
Skin
  Rash 1.4 (0.4) 0.4

Heart Failure

Adverse experiences occurring in greater than one percent of patients with heart failure treated with VASOTEC are shown below. The incidences represent the experiences from both controlled and uncontrolled clinical trials (maximum duration of therapy was approximately one year). In the placebo treated patients, the incidences reported are from the controlled trials (maximum duration of therapy is 12 weeks). The percentage of patients with severe heart failure (NYHA Class IV) was 29 percent and 43 percent for patients treated with VASOTEC and placebo, respectively.

  VASOTEC
(n=673) Incidence (discontinuation)
Placebo
(n=339) Incidence
Body As A Whole
  Orthostatic Effects 2.2 (0.1) 0.3
  Syncope 2.2 (0.1) 0.9
  Chest Pain 2.1 (0.0) 2.1
  Fatigue 1.8 (0.0) 1.8
  Abdominal Pain 1.6 (0.4) 2.1
  Asthenia 1.6 (0.1) 0.3
Cardiovascular
  Hypotension   6.7 (1.9) 0.6
  Orthostatic Hypotension 1.6 (0.1) 0.3
  Angina Pectoris 1.5 (0.1) 1.8
  Myocardial Infarction 1.2 (0.3) 1.8
Digestive
  Diarrhea 2.1 (0.1) 1.2
  Nausea 1.3 (0.1) 0.6
  Vomiting 1.3 (0.0) 0.9
Nervous/Psychiatric
  Dizziness 7.9 (0.6) 0.6
  Headache 1.8 (0.1) 0.9
  Vertigo 1.6 (0.1) 1.2
Respiratory
  Cough 2.2 (0.0) 0.6
  Bronchitis 1.3 (0.0) 0.9
  Dyspnea 1.3 (0.1) 0.4
  Pneumonia 1.0 (0.0) 2.4
Skin
  Rash 1.3 (0.0) 2.4
Urogenital
  Urinary Tract Infection 1.3 (0.0) 2.4

Other serious clinical adverse experiences occurring since the drug was marketed or adverse experiences occurring in 0.5 to 1.0 percent of patients with hypertension or heart failure in clinical trials are listed below and, within each category, are in order of decreasing severity.

Body As A Whole: Anaphylactoid reactions (see WARNINGS, Anaphylactoid and Possibly Related Reactions).

Cardiovascular: Cardiac arrest; myocardial infarction or cerebrovascular accident, possibly secondary to excessive hypotension in high risk patients (see WARNINGS, Hypotension); pulmonary embolism and infarction; pulmonary edema; rhythm disturbances including atrial tachycardia and bradycardia; atrial fibrillation; palpitation, Raynaud's phenomenon.

Digestive: Ileus, pancreatitis, hepatic failure, hepatitis (hepatocellular [proven on rechallenge] or cholestatic jaundice) (see WARNINGS, Hepatic Failure), melena, anorexia, dyspepsia, constipation, glossitis, stomatitis, dry mouth.

Hematologic: Rare cases of neutropenia, thrombocytopenia and bone marrow depression.

Musculoskeletal: Muscle cramps.

Nervous/Psychiatric: Depression, confusion, ataxia, somnolence, insomnia, nervousness, peripheral neuropathy (e.g., paresthesia, dysesthesia), dream abnormality.

Respiratory: Bronchospasm, rhinorrhea, sore throat and hoarseness, asthma, upper respiratory infection, pulmonary infiltrates, eosinophilic pneumonitis.

Skin: Exfoliative dermatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, pemphigus, herpes zoster, erythema multiforme, urticaria, pruritus, alopecia, flushing, diaphoresis, photosensitivity.

Special Senses: Blurred vision, taste alteration, anosmia, tinnitus, conjunctivitis, dry eyes, tearing.

Urogenital: Renal failure, oliguria, renal dysfunction (see PRECAUTIONS and DOSAGE AND ADMINISTRATION), flank pain, gynecomastia, impotence.

Miscellaneous: A symptom complex has been reported which may include some or all of the following: a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia/myositis, fever, serositis, vasculitis, leukocytosis, eosinophilia, photosensitivity, rash and other dermatologic manifestations.

Angioedema: Angioedema has been reported in patients receiving VASOTEC, 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 VASOTEC should be discontinued and appropriate therapy instituted immediately (see WARNINGS).

Hypotension: In the hypertensive patients, hypotension occurred in 0.9 percent and syncope occurred in 0.5 percent of patients following the initial dose or during extended therapy. Hypotension or syncope was a cause for discontinuation of therapy in 0.1 percent of hypertensive patients. In heart failure patients, hypotension occurred in 6.7 percent and syncope occurred in 2.2 percent of patients. Hypotension or syncope was a cause for discontinuation of therapy in 1.9 percent of patients with heart failure (see WARNINGS).

Cough: See PRECAUTIONS, Cough.

Pediatric Patients

The adverse experience profile for pediatric patients appears to be similar to that seen in adult patients.

Clinical Laboratory Test Findings

Serum Electrolytes

Hyperkalemia (see PRECAUTIONS), hyponatremia.

Creatinine, Blood Urea Nitrogen

In controlled clinical trials minor increases in blood urea nitrogen and serum creatinine, reversible upon discontinuation of therapy, were observed in about 0.2 percent of patients with essential hypertension treated with VASOTEC alone. Increases are more likely to occur in patients receiving concomitant diuretics or in patients with renal artery stenosis (see PRECAUTIONS). In patients with heart failure who were also receiving diuretics with or without digitalis, increases in blood urea nitrogen or serum creatinine, usually reversible upon discontinuation of VASOTEC and/or other concomitant diuretic therapy, were observed in about 11 percent of patients. Increases in blood urea nitrogen or creatinine were a cause for discontinuation in 1.2 percent of patients.

Hematology

Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.3 g percent and 1.0 vol percent, respectively) occur frequently in either hypertension or congestive heart failure patients treated with VASOTEC but are rarely of clinical importance unless another cause of anemia coexists. In clinical trials, less than 0.1 percent of patients discontinued therapy due to anemia. Hemolytic anemia, including cases of hemolysis in patients with G-6-PD deficiency, has been reported; a causal relationship to enalapril cannot be excluded.

Liver Function Tests

Elevations of liver enzymes and/or serum bilirubin have occurred (see WARNINGS, Hepatic Failure).

Read the Vasotec (enalapril) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

Dual Blockade of the Renin-Angiotensin System (RAS)

Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Closely monitor blood pressure, renal function and electrolytes in patients on Vasotec and other agents that affect the RAS.

Do not co-administer aliskiren with Vasotec in patients with diabetes. Avoid use of aliskiren with Vasotec in patients with renal impairment (GFR < 60 ml/min).

Hypotension — Patients on Diuretic Therapy

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 enalapril. The possibility of hypotensive effects with enalapril can be minimized by either discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with enalapril. If it is necessary to continue the diuretic, provide close medical supervision after the initial dose for at least two hours and until blood pressure has stabilized for at least an additional hour (see WARNINGS and DOSAGE AND ADMINISTRATION).

Agents Causing Renin Release

The antihypertensive effect of VASOTEC is augmented by antihypertensive agents that cause renin release (e.g., diuretics).

Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors)

In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including enalapril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving enalapril and NSAID therapy.

In a clinical pharmacology study, indomethacin or sulindac was administered to hypertensive patients receiving VASOTEC. In this study there was no evidence of a blunting of the antihypertensive action of VASOTEC. However, reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors.

Other Cardiovascular Agents

VASOTEC has been used concomitantly with beta adrenergic-blocking agents, methyldopa, nitrates, calcium-blocking agents, hydralazine, prazosin and digoxin without evidence of clinically significant adverse interactions.

Agents Increasing Serum Potassium

VASOTEC attenuates potassium loss caused by thiazide-type diuretics. Potassium-sparing diuretics (e.g., spironolactone, 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 receiving VASOTEC.

Lithium

Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs which cause elimination of sodium, including ACE inhibitors. A few cases of lithium toxicity have been reported in patients receiving concomitant VASOTEC and lithium and were reversible upon discontinuation of both drugs. It is recommended that serum lithium levels be monitored frequently if enalapril is administered concomitantly with lithium.

Gold

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 VASOTEC.

Last reviewed on RxList: 9/24/2012
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

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 VASOTEC) 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 VASOTEC. This may occur at any time during treatment. In such cases VASOTEC 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 (see ADVERSE REACTIONS).

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.

Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see also INDICATIONS AND USAGE and CONTRAINDICATIONS).

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 VASOTEC alone. Patients with heart failure given VASOTEC 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 (see DOSAGE AND ADMINISTRATION). 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 VASOTEC in patients at risk for excessive hypotension who are able to tolerate such adjustments (see PRECAUTIONS: DRUG INTERACTIONS and ADVERSE REACTIONS). 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 VASOTEC, which usually can be given without difficulty once the blood pressure has stabilized. If symptomatic hypotension develops, a dose reduction or discontinuation of VASOTEC 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 toxicity

Pregnancy category D

Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Vasotec 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 reninangiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.

In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue VASOTEC, 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 VASOTEC for hypotension, oliguria, and hyperkalemia. [see PRECAUTIONS, Pediatric use]

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).

PRECAUTIONS

General

Aortic Stenosis/Hypertrophic Cardiomyopathy:

As with all vasodilators, enalapril 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 heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin converting enzyme inhibitors, including VASOTEC, may be associated with oliguria and/or progressive azotemia and rarely with acute renal failure and/or death. (see PRECAUTIONS: DRUG INTERACTIONS)

In clinical studies in hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine were observed in 20 percent of patients. These increases were almost always reversible upon discontinuation of enalapril 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 and serum creatinine, usually minor and transient, especially when VASOTEC 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 VASOTEC may be required.

Evaluation of patients with hypertension or heart failure should always include assessment of renal function (see DOSAGE AND ADMINISTRATION).

Hyperkalemia

Elevated serum potassium (greater than 5.7 mEq/L) was observed in approximately one percent of hypertensive patients in clinical trials. In most cases these were isolated values which resolved despite continued therapy. Hyperkalemia was a cause of discontinuation of therapy in 0.28 percent of hypertensive patients. In clinical trials in heart failure, hyperkalemia was observed in 3.8 percent of patients but was not a cause for discontinuation.

Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassiumsparing diuretics, potassium supplements and/or potassium- containing salt substitutes, which should be used cautiously, if at all, with VASOTEC (see DRUG INTERACTIONS).

Cough

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.

Surgery/Anesthesia

In patients undergoing major surgery or during anesthesia with agents that produce hypotension, enalapril 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

There was no evidence of a tumorigenic effect when enalapril was administered for 106 weeks to male and female rats at doses up to 90 mg/kg/day or for 94 weeks to male and female mice at doses up to 90 and 180 mg/kg/day, respectively. These doses are 26 times (in rats and female mice) and 13 times (in male mice) the maximum recommended human daily dose (MRHDD) when compared on a body surface area basis.

Neither enalapril maleate nor the active diacid was mutagenic in the Ames microbial mutagen test with or without metabolic activation. Enalapril was also negative in the following genotoxicity studies: rec-assay, reverse mutation assay with E. coli, sister chromatid exchange with cultured mammalian cells, and the micronucleus test with mice, as well as in an in vivo cytogenic study using mouse bone marrow.

There were no adverse effects on reproductive performance of male and female rats treated with up to 90 mg/kg/day of enalapril (26 times the MRHDD when compared on a body surface area basis).

Pregnancy

Nursing Mothers

Enalapril and enalaprilat have been detected in human breast milk. Because of the potential for serious adverse reactions in nursing infants from enalapril, a decision should be made whether to discontinue nursing or to discontinue VASOTEC, taking into account the importance of the drug to the mother.

Pediatric Use

Neonates with a history of in utero exposure to VASOTEC

If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfustions or dialysis may be required as a 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.

Antihypertensive effects of VASOTEC have been established in hypertensive pediatric patients age 1 month to 16 years. Use of VASOTEC in these age groups is supported by evidence from adequate and well-controlled studies of VASOTEC in pediatric and adult patients as well as by published literature in pediatric patients (see CLINICAL PHARMACOLOGY, CLINICAL PHARMACOLOGY in Pediatric Patients and DOSAGE AND ADMINISTRATION).

VASOTEC is not recommended in neonates and in pediatric patients with glomerular filtration rate < 30 mL/min/1.73 m2, as no data are available.

Last reviewed on RxList: 9/24/2012
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

Limited data are available in regard to overdosage in humans.

Single oral doses of enalapril above 1,000 mg/kg and ≥ 1,775 mg/kg were associated with lethality in mice and rats, respectively.

The most likely manifestation of overdosage would be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution.

Enalaprilat may be removed from general circulation by hemodialysis and has been removed from neonatal circulation by peritoneal dialysis (see WARNINGS, Anaphylactoid reactions during membrane exposure).

CONTRAINDICATIONS

VASOTEC 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.

Do not co-administer aliskiren with Vasotec in patients with diabetes (see PRECAUTIONS: DRUG INTERACTIONS).

Last reviewed on RxList: 9/24/2012
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Enalapril, after hydrolysis to enalaprilat, inhibits angiotensin-converting enzyme (ACE) in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. The beneficial effects of enalapril in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system. Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion. Although the latter decrease is small, it results in small increases of serum potassium. In hypertensive patients treated with VASOTEC alone for up to 48 weeks, mean increases in serum potassium of approximately 0.2 mEq/L were observed. In patients treated with VASOTEC plus a thiazide diuretic, there was essentially no change in serum potassium (see PRECAUTIONS). Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity.

ACE is identical to kininase, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of VASOTEC remains to be elucidated.

While the mechanism through which VASOTEC lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, VASOTEC is antihypertensive even in patients with low-renin hypertension. Although VASOTEC was antihypertensive in all races studied, black hypertensive patients (usually a low-renin hypertensive population) had a smaller average response to enalapril monotherapy than non-black patients.

Pharmacokinetics and Metabolism

Following oral administration of VASOTEC, peak serum concentrations of enalapril occur within about one hour. Based on urinary recovery, the extent of absorption of enalapril is approximately 60 percent. Enalapril absorption is not influenced by the presence of food in the gastrointestinal tract. Following absorption, enalapril is hydrolyzed to enalaprilat, which is a more potent angiotensin converting enzyme inhibitor than enalapril; enalaprilat is poorly absorbed when administered orally. Peak serum concentrations of enalaprilat occur three to four hours after an oral dose of enalapril maleate. Excretion of VASOTEC is primarily renal. Approximately 94 percent of the dose is recovered in the urine and feces as enalaprilat or enalapril. The principal components in urine are enalaprilat, accounting for about 40 percent of the dose, and intact enalapril. There is no evidence of metabolites of enalapril, other than enalaprilat.

The serum concentration profile of enalaprilat exhibits a prolonged terminal phase, apparently representing a small fraction of the administered dose that has been bound to ACE. The amount bound does not increase with dose, indicating a saturable site of binding. The effective half-life for accumulation of enalaprilat following multiple doses of enalapril maleate is 11 hours. The disposition of enalapril and enalaprilat in patients with renal insufficiency is similar to that in patients with normal renal function until the glomerular filtration rate is 30 mL/min or less. With glomerular filtration rate ≤ 30 mL/min, peak and trough enalaprilat levels increase, time to peak concentration increases and time to steady state may be delayed. The effective half-life of enalaprilat following multiple doses of enalapril maleate is prolonged at this level of renal insufficiency (see DOSAGE AND ADMINISTRATION). Enalaprilat is dialyzable at the rate of 62 mL/min.

Studies in dogs indicate that enalapril crosses the blood-brain barrier poorly, if at all; enalaprilat does not enter the brain. Multiple doses of enalapril maleate in rats do not result in accumulation in any tissues. Milk of lactating rats contains radioactivity following administration of 14Cenalapril maleate. Radioactivity was found to cross the placenta following administration of labeled drug to pregnant hamsters.

Pharmacodynamics and Clinical Effects

Hypertension

Administration of VASOTEC to patients with hypertension of severity ranging from mild to severe results in a reduction of both supine and standing blood pressure usually with no orthostatic component. Symptomatic postural hypotension is therefore infrequent, although it might be anticipated in volume-depleted patients (see WARNINGS).

In most patients studied, after oral administration of a single dose of enalapril, onset of antihypertensive activity was seen at one hour with peak reduction of blood pressure achieved by four to six hours.

At recommended doses, antihypertensive effects have been maintained for at least 24 hours. In some patients the effects may diminish toward the end of the dosing interval (see DOSAGE AND ADMINISTRATION).

In some patients achievement of optimal blood pressure reduction may require several weeks of therapy.

The antihypertensive effects of VASOTEC have continued during long term therapy. Abrupt withdrawal of VASOTEC has not been associated with a rapid increase in blood pressure.

In hemodynamic studies in patients with essential hypertension, blood pressure reduction was accompanied by a reduction in peripheral arterial resistance with an increase in cardiac output and little or no change in heart rate. Following administration of VASOTEC, there is an increase in renal blood flow; glomerular filtration rate is usually unchanged. The effects appear to be similar in patients with renovascular hypertension.

When given together with thiazide-type diuretics, the blood pressure lowering effects of VASOTEC are approximately additive.

In a clinical pharmacology study, indomethacin or sulindac was administered to hypertensive patients receiving VASOTEC. In this study there was no evidence of a blunting of the antihypertensive action of VASOTEC (see PRECAUTIONS: DRUG INTERACTIONS).

Heart Failure

In trials in patients treated with digitalis and diuretics, treatment with enalapril resulted in decreased systemic vascular resistance, blood pressure, pulmonary capillary wedge pressure and heart size, and increased cardiac output and exercise tolerance. Heart rate was unchanged or slightly reduced, and mean ejection fraction was unchanged or increased. There was a beneficial effect on severity of heart failure as measured by the New York Heart Association (NYHA) classification and on symptoms of dyspnea and fatigue. Hemodynamic effects were observed after the first dose, and appeared to be maintained in uncontrolled studies lasting as long as four months. Effects on exercise tolerance, heart size, and severity and symptoms of heart failure were observed in placebo-controlled studies lasting from eight weeks to over one year.

Heart Failure, Mortality Trials

In a multicenter, placebo-controlled clinical trial, 2,569 patients with all degrees of symptomatic heart failure and ejection fraction ≤ 35 percent were randomized to placebo or enalapril and followed for up to 55 months (SOLVD-Treatment). Use of enalapril was associated with an 11 percent reduction in all-cause mortality and a 30 percent reduction in hospitalization for heart failure. Diseases that excluded patients from enrollment in the study included severe stable angina ( > 2 attacks/day), hemodynamically significant valvular or outflow tract obstruction, renal failure (creatinine > 2.5 mg/dL), cerebral vascular disease (e.g., significant carotid artery disease), advanced pulmonary disease, malignancies, active myocarditis and constrictive pericarditis. The mortality benefit associated with enalapril does not appear to depend upon digitalis being present.

A second multicenter trial used the SOLVD protocol for study of asymptomatic or minimally symptomatic patients. SOLVD-Prevention patients, who had left ventricular ejection fraction ≤ 35% and no history of symptomatic heart failure, were randomized to placebo (n=2117) or enalapril (n=2111) and followed for up to 5 years. The majority of patients in the SOLVD-Prevention trial had a history of ischemic heart disease. A history of myocardial infarction was present in 80 percent of patients, current angina pectoris in 34 percent, and a history of hypertension in 37 percent. No statistically significant mortality effect was demonstrated in this population. Enalapril-treated subjects had 32% fewer first hospitalizations for heart failure, and 32% fewer total heart failure hospitalizations. Compared to placebo, 32 percent fewer patients receiving enalapril developed symptoms of overt heart failure. Hospitalizations for cardiovascular reasons were also reduced. There was an insignificant reduction in hospitalizations for any cause in the enalapril treatment group (for enalapril vs. placebo, respectively, 1166 vs. 1201 first hospitalizations, 2649 vs. 2840 total hospitalizations), although the study was not powered to look for such an effect.

The SOLVD-Prevention trial was not designed to determine whether treatment of asymptomatic patients with low ejection fraction would be superior, with respect to preventing hospitalization, to closer follow-up and use of enalapril at the earliest sign of heart failure. However, under the conditions of follow-up in the SOLVD-Prevention trial (every 4 months at the study clinic; personal physician as needed), 68% of patients on placebo who were hospitalized for heart failure had no prior symptoms recorded which would have signaled initiation of treatment.

The SOLVD-Prevention trial was also not designed to show whether enalapril modified the progression of underlying heart disease.

In another multicenter, placebo-controlled trial (CONSENSUS) limited to patients with NYHA Class IV congestive heart failure and radiographic evidence of cardiomegaly, use of enalapril was associated with improved survival. The results are shown in the following table.

  SURVIVAL (%)
Six Months One Year
VASOTEC (n=127) 74 64
Placebo (n-126) 56 48

In both CONSENSUS and SOLVD-Treatment trials, patients were also usually receiving digitalis, diuretics or both.

Clinical Pharmacology in Pediatric Patients

A multiple dose pharmacokinetic study was conducted in 40 hypertensive male and female pediatric patients aged 2 months to ≤ 16 years following daily oral administration of 0.07 to 0.14 mg/kg enalapril maleate. At steady state, the mean effective half-life for accumulation of enalaprilat was 14 hours and the mean urinary recovery of total enalapril and enalaprilat in 24 hours was 68% of the administered dose. Conversion of enalapril to enalaprilat was in the range of 63-76%. The overall results of this study indicate that the pharmacokinetics of enalapril in hypertensive children aged 2 months to ≤ 16 years are consistent across the studied age groups and consistent with pharmacokinetic historic data in healthy adults.

In a clinical study involving 110 hypertensive pediatric patients 6 to 16 years of age, patients who weighed < 50 kg received either 0.625, 2.5 or 20 mg of enalapril daily and patients who weighed ≥ 50 kg received either 1.25, 5, or 40 mg of enalapril daily. Enalapril administration once daily lowered trough blood pressure in a dose-dependent manner. The dose-dependent antihypertensive efficacy of enalapril was consistent across all subgroups (age, Tanner stage, gender, race). However, the lowest doses studied, 0.625 mg and 1.25 mg, corresponding to an average of 0.02 mg/kg once daily, did not appear to offer consistent antihypertensive efficacy. In this study, VASOTEC was generally well tolerated.

In the above pediatric studies, enalapril maleate was given as tablets of VASOTEC and for those children and infants who were unable to swallow tablets or who required a lower dose than is available in tablet form, enalapril was administered in a suspension formulation (see Preparation of Suspension under DOSAGE AND ADMINISTRATION).

Last reviewed on RxList: 9/24/2012
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Angioedema

Angioedema, including laryngeal edema, may occur at any time during treatment with angiotensin converting enzyme inhibitors, including enalapril. 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.

Hypotension

Patients should be cautioned to report lightheadedness, especially during the first few days of therapy. If actual syncope occurs, the patients 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 the physician.

Hyperkalemia

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

Neutropenia

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

Pregnancy

Female patients of childbearing age should be told about the consequences of exposure to VASOTEC during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible.

NOTE: As with many other drugs, certain advice to patients being treated with enalapril is warranted. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.

Last reviewed on RxList: 9/24/2012
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

Angioedema

Angioedema, including laryngeal edema, may occur at any time during treatment with angiotensin converting enzyme inhibitors, including enalapril. 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.

Hypotension

Patients should be cautioned to report lightheadedness, especially during the first few days of therapy. If actual syncope occurs, the patients 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 the physician.

Hyperkalemia

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

Neutropenia

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

Pregnancy

Female patients of childbearing age should be told about the consequences of exposure to VASOTEC during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible.

NOTE: As with many other drugs, certain advice to patients being treated with enalapril is warranted. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.

Last reviewed on RxList: 9/24/2012
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Vasotec Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

ENALAPRIL - ORAL

(e-NAL-a-pril)

COMMON BRAND NAME(S): Vasotec

WARNING: This drug can cause serious (possibly fatal) harm to an unborn baby if used during pregnancy. Therefore, it is important to prevent pregnancy while taking this medication. Consult your doctor for more details and to discuss the use of reliable forms of birth control while taking this medication. If you are planning pregnancy, become pregnant, or think you may be pregnant, contact your doctor immediately.

USES: Enalapril is used to treat high blood pressure (hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. It is also used to treat heart failure.

Enalapril is an ACE inhibitor and works by relaxing blood vessels so that blood can flow more easily.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This medication may also be used to help protect the kidneys from harm due to diabetes.

HOW TO USE: Take this medication by mouth with or without food as directed by your doctor, usually once or twice daily.

If you are using the suspension form of this medication, shake the bottle well before each dose. Carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose.

The dosage is based on your medical condition and response to treatment. For children, the dosage is also based on weight.

Use this medication regularly in order to get the most benefit from it. To help you remember, take it at the same time(s) each day. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick.

For the treatment of high blood pressure, it may take several weeks before you get the full benefit of this medication. For the treatment of heart failure, it may take weeks to months before you get the full benefit of this medication. Tell your doctor if your condition does not improve or if it worsens (such as your blood pressure readings remain high or increase).

Disclaimer

Vasotec Consumer (continued)

SIDE EFFECTS: Dizziness, lightheadedness, or weakness may occur as your body adjusts to the medication. Dry cough may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if any of these unlikely but serious side effects occur: fainting, muscle weakness, signs of infection (such as fever, chills, persistent sore throat), change in the amount of urine.

This drug may rarely cause serious (possibly fatal) liver problems. Tell your doctor right away if you notice any of the following rare but serious side effects: yellowing eyes/skin, dark urine, severe stomach/abdominal pain, persistent nausea/vomiting.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Vasotec (enalapril) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking enalapril, tell your doctor or pharmacist if you are allergic to it; or to other ACE inhibitors (such as benazepril); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: history of an allergic reaction which included swelling of the face/lips/tongue/throat (angioedema), blood filtering procedures (such as LDL apheresis, dialysis), high level of potassium in the blood, collagen vascular disease (such as lupus, scleroderma).

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Too much sweating, diarrhea, or vomiting may cause loss of too much body water (dehydration) and increase your risk of lightheadedness. Report prolonged diarrhea or vomiting to your doctor. Be sure to drink enough fluids to prevent dehydration unless your doctor directs you otherwise.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

This product may increase your potassium levels. Before using potassium supplements or salt substitutes that contain potassium, consult your doctor or pharmacist.

Older adults may be more sensitive to the effects of this product, especially dizziness.

This medication is not recommended for use during pregnancy. It may harm an unborn baby. Consult your doctor for more details. (See also Warning section.)

This medication passes into breast milk but is unlikely to harm a nursing infant. Consult your doctor before breast-feeding.

Disclaimer

Vasotec Consumer (continued)

DRUG INTERACTIONS: See also Precautions section.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: aliskiren, lithium, drugs that may increase your potassium level (including birth control products that contain drospirenone).

Check the labels on all your medicines (such as cough-and-cold products, diet aids, or NSAIDs such as ibuprofen, naproxen) because they may contain ingredients that could increase your blood pressure or worsen your heart failure. Ask your pharmacist for more details.

A very serious reaction may occur if you are getting injections for bee/wasp sting allergy (desensitization) and are also taking enalapril. Make sure all your doctors know which medicines you are using.

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe dizziness, fainting.

NOTES: Do not share this medication with others.

Lifestyle changes such as stress reduction programs, exercise and dietary changes may increase the effectiveness of this medicine. Talk to your doctor or pharmacist about lifestyle changes that might benefit you.

Laboratory and/or medical tests (such as kidney function, potassium levels) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

Check your blood pressure regularly while taking this medication. Learn how to monitor your own blood pressure at home, and share the results with your doctor.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store tablets at room temperature away from light and moisture. Store the suspension in the refrigerator. Discard any unused suspension after 30 days. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised April 2012. Copyright(c) 2012 First Databank, Inc.

Vasotec Patient Information Including Side Effects

Brand Names: Vasotec

Generic Name: enalapril (Pronunciation: e NAL a pril)

What is enalapril (Vasotec)?

Enalapril is in a group of drugs called ACE inhibitors. ACE stands for angiotensin converting enzyme.

Enalapril is used to treat high blood pressure (hypertension), congestive heart failure, kidney problems caused by diabetes, and to improve survival after a heart attack.

Enalapril may also be used for other purposes not listed in this medication guide.

Enalapril 10 mg-APO

round, red, imprinted with APO 051

Enalapril 10 mg-EON

round, pink, imprinted with E 147

Enalapril 10 mg-GEN

round, pink, imprinted with GG 483

Enalapril 10 mg-MYL

round, blue, imprinted with M E17

Enalapril 10 mg-SAN

round, pink, imprinted with ELP 10

Enalapril 10 mg-SCH

round, pink, imprinted with SCHN, 2727

Enalapril 10 mg-TAR

round, pink, imprinted with T 10

Enalapril 10 mg-TEV

oval, pink, imprinted with 93 28

Enalapril 10 mg-WAT

round, pink/white specks, imprinted with WATSON 670

Enalapril 2.5 mg-APO

round, yellow, imprinted with APO 049

Enalapril 2.5 mg-EON

round, yellow, imprinted with E 114

Enalapril 2.5 mg-MYL

round, white, imprinted with M E15

Enalapril 2.5 mg-PAR

round, white, imprinted with EN 25, G

Enalapril 2.5 mg-SAN

round, yellow, imprinted with ELP 2 1/2

Enalapril 2.5 mg-SCH

round, white, imprinted with SCHN, 26 98

Enalapril 2.5 mg-TAR

round, yellow, imprinted with T 2

Enalapril 2.5 mg-TEV

oval, yellow, imprinted with 93 26

Enalapril 2.5 mg-WAT

round, white, imprinted with WATSON 668

Enalapril 20 mg-APO

rectangular, orange, imprinted with APO 052

Enalapril 20 mg-EON

round, pink, imprinted with E 214

Enalapril 20 mg-MYL

round, blue, imprinted with M E18

Enalapril 20 mg-PAR

oval, peach, imprinted with G, EN 20

Enalapril 20 mg-SAN

round, gray, imprinted with ELP 20

Enalapril 20 mg-SCH

round, pink, imprinted with SCHN, 2734

Enalapril 20 mg-TAR

round, peach, imprinted with T 20

Enalapril 20 mg-TEV

oval, peach, imprinted with 93 29

Enalapril 20 mg-WAT

round, peach/white specks, imprinted with WATSON 671

Enalapril 5 mg-APO

round, white, imprinted with APO 050

Enalapril 5 mg-EON

round, white, imprinted with E 127

Enalapril 5 mg-GEN

round, white, imprinted with GG 482

Enalapril 5 mg-MYL

round, white, imprinted with M E16

Enalapril 5 mg-SAN

round, pink, imprinted with ELP 5

Enalapril 5 mg-SCH

round, white, imprinted with SCHN, 27 01

Enalapril 5 mg-TAR

round, yellow, imprinted with T 5

Enalapril 5 mg-TEV

oval, white, imprinted with 93 27

Enalapril 5 mg-WAT

round, white, imprinted with WATSON 669

Vasotec 10 mg

shield, pink, imprinted with VASOTEC, MSD 713

Vasotec 10 mg-BTA

triangular, orange, imprinted with VASO 10

Vasotec 2.5 mg

shield, yellow, imprinted with VASOTEC, MSD 14

Vasotec 2.5 mg-BTA

oval, white, imprinted with VASO 2.5

Vasotec 20 mg

shield, beige, imprinted with VASOTEC, MSD 714

Vasotec 20 mg-BTA

triangular, yellow, imprinted with VASO 20

Vasotec 5 mg

shield, white, imprinted with VASOTEC, MSD 712

Vasotec 5 mg-BTA

triangular, white, imprinted with VASO 5

What are the possible side effects of enalapril (Vasotec)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; severe stomach pain; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • feeling light-headed, fainting;
  • urinating more or less than usual, or not at all;
  • fever, chills, body aches, flu symptoms;
  • pale skin, easy bruising or bleeding;
  • fast, pounding, or uneven heartbeats;
  • chest pain; or
  • swelling, rapid weight gain.

Less serious side effects may include:

  • cough;
  • loss of taste sensation, loss of appetite;
  • dizziness, drowsiness, headache;
  • sleep problems (insomnia);
  • dry mouth;
  • nausea, vomiting, diarrhea; or
  • mild skin itching or rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Vasotec (enalapril) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about enalapril (Vasotec)?

Vomiting, diarrhea, or heavy sweating can cause you to become dehydrated. This can lead to very low blood pressure, electrolyte disorders, or kidney failure while you are taking enalapril. Drink plenty of water each day while you are taking this medication.

Side Effects Centers

Vasotec Patient Information including How Should I Take

What should I discuss with my healthcare provider before taking enalapril (Vasotec)?

Do not use this medication if you are allergic to enalapril or to any other ACE inhibitor, such as benazepril (Lotensin), captopril (Capoten), fosinopril (Monopril), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), or trandolapril (Mavik).

If you have any of these other conditions, you may need a dose adjustment or special tests to safely take enalapril:

  • kidney disease (or if you are on dialysis);
  • liver disease;
  • heart disease or congestive heart failure;
  • diabetes; or
  • a connective tissue disease such as Marfan syndrome, Sjogren's syndrome, lupus, scleroderma, or rheumatoid arthritis.

FDA pregnancy category D. Do not use this medication without telling your doctor if you are pregnant or planning a pregnancy. Enalapril could cause birth defects in the baby if you take the medication during pregnancy. Use an effective form of birth control. Stop using this medication and tell your doctor right away if you become pregnant during treatment.

Enalapril can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take enalapril (Vasotec)?

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results from this medication.

Take each dose with a full glass of water.

Enalapril can be taken with or without food.

Vomiting, diarrhea, or heavy sweating can cause you to become dehydrated. This can lead to very low blood pressure, electrolyte disorders, or kidney failure while you are taking enalapril. Drink plenty of water each while you are taking this medication.

To be sure this medication is helping your condition, your blood pressure will need to be checked on a regular basis. Your kidney or liver function may also need to be tested. Do not miss any scheduled visits to your doctor.

If you need to have any type of surgery, tell the surgeon ahead of time that you are taking enalapril. You may need to stop using the medicine for a short time.

If you are being treated for high blood pressure, keep using this medication even if you feel fine. High blood pressure often has no symptoms.

Store enalapril at room temperature away from moisture and heat.

Side Effects Centers

Vasotec Patient Information including If I Miss a Dose

What happens if I miss a dose (Vasotec)?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Vasotec)?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include feeling extremely dizzy or light-headed, or fainting.

What should I avoid while taking enalapril (Vasotec)?

Avoid drinking alcohol. It can further lower your blood pressure and may increase some of the side effects of enalapril.

Do not use salt substitutes or potassium supplements while taking enalapril, unless your doctor has told you to.

What other drugs will affect enalapril (Vasotec)?

Before taking enalapril, tell your doctor if you are taking any of the following drugs:

  • gold injections to treat arthritis;
  • lithium (Lithobid, Eskalith);
  • a potassium supplement such as K-Dur, Klor-Con;
  • salt substitutes that contain potassium;
  • aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) such as ibuprofen (Motrin, Advil), diclofenac (Voltaren), etodolac (Lodine), indomethacin (Indocin), ketoprofen (Orudis), naproxen (Aleve, Naprosyn), and others; or
  • a diuretic (water pill).

This list is not complete and there may be other drugs that can interact with enalapril. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about enalapril.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 6.04. Revision date: 12/15/2010.

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