Zestril
Zestril Medication Information:
Zestril medication comes in several different strengths; click on the strength you need to view prices from pharmacies competing to earn your business.
|
Zestril 2.500 mg
|
Zestril 5 mg
|
Zestril 10 mg
|
|
Zestril 20 mg
|
Zestril 40 mg
|
Zestril Information
Zestril is in the group of drugs known as ACE inhibitors. It is often used to treat high blood pressure (hypertension), congestive heart failure, and can be used after a heart attack to improve chances of survival.
How does Zestril Work
Zestril works by relaxing the blood vessels and helping the heart to pump blood that carries the oxygen to different parts of the body more efficiently. When these blood vessels relax, they widen and the overall effect is a drop in blood pressure. This reduced drop in blood pressure means the body doesn't have to work as hard when pumping blood. When used immediately after a heart attack, it can also significantly lower the risks of having another heart attack. It has also been approved, and is safe, for use in children 6 years and older. While Zestril does help in these conditions, it does not cure them, and the medication will need to be continued even after symptoms lessen.
How to take Zestril
Depending on the condition being treated, the usual dosage for Zestril ranges from 2.5mg to 40mg daily, and is taken once daily, with or without food. The dosage prescribed is influenced by weight, medical conditions, and other medications being taken. People taking other medications for high blood pressure take lower doses. Zestril should be taken regularly, but if a dosage is missed, you should take it as soon as possible. However, if it is almost time for your next dosage, you should just skip the dosage all together. It can take up for two weeks for results to be recognized.
Side Effects
There are some common side effects of this drug. Sometimes as the body gets used to the drug the side effects will go away on their own. Some of these side effects may include a dry, persistent cough, and headaches. Some of the less common side effects of Zestril are diarrhea, nausea, a loss of taste, and unusual tiredness. There are also some less common side effects sometimes seen, and your physician should be contacted if any of these arise. They include, fainting, skin rashes, abdominal pain, and chest pains. Medical attention should be immediately sought if any of the following occur, fever and chills, swelling of hands, face, mouth or feet, and sudden trouble swallowing or breathing.
Other Names for Zestril
- Lisinopril
- Prinivil
Safety Information:
The medication Zestril should not be taken if you have had a previous allergic reaction to it, or any of the other ACE inhibitors. If you have been diagnosed with idiopathic or hereditary angioedema (swelling of the hands, face, lips, eyes, throat, or tongue; difficulty swallowing or breathing; or hoarseness) you should also avoid taking this medication. People who have kidney disease, maintain high levels of potassium in their blood, or have diabetes may also in counter problems when taking Zestril, so a physician should be informed before you begin taking it. Zestril is classified as a pregnancy drug "D," so women who are pregnant or nursing should also avoid this drug.
Dosage:
Zestril Dosages Available
- 2.5mg capsule
- 5mg capsule
- 10mg capsule
- 20 mg capsule
- 40 mg capsule
Visual Description:
When prescribed as Zestril the capsules are round or shield shaped, and can be found in pink, white, red, or yellow. They will have Zestril imprinted on one side.
Zestril Facts
Zestril is manufactured by IPR Pharmaceuticals, Inc, for AstraZeneca Pharmaceuticals LP.
How well patients tolerate Zestril therapy was evaluated in controlled clinical trials.
Clinical trials evaluated Zestril treatment in 1,969 patients diagnosed with hypertension or heart failure.
Zestril obtained original or tentative approval from the FDA on May 19, 1988.
Pharmacology
Pharmacokinetics
After oral administration of ZESTRIL (lisinopril), peak serum concentrations of lisinopril occur within approximately 7 hours, although patients with recent myocardial infarction have demonstrated an increase in time to peak serum concentration to about 8 to 10 hours. Declining serum concentrations exhibit a prolonged terminal phase which does not contribute to drug accumulation. This terminal phase probably represents saturable binding to ACE and is not proportional to dose. Lisinopril does not bind serum proteins other than ACE.
Lisinopril does not undergo metabolism and is excreted unchanged entirely in the urine. Based on urinary recovery, the extent of absorption of lisinopril is approximately 25%, with large inter-subject variability (6-60%) at all doses tested (5-80 mg).
Lisinopril absorption is not influenced by the presence of food in the gastrointestinal tract.
Following multiple doses of lisinopril, the effective half-life of accumulation is 12 hours.
In a study in elderly healthy subjects (65 years and above), a single dose of lisinopril 20 mg produced higher serum concentrations and higher values for the area under the plasma curve than those seen in young healthy adults given a similar dose. In another study, single daily doses of lisinopril 5 mg were given for 7 consecutive days to young and elderly healthy volunteers and to elderly patients with congestive heart failure. Maximum serum concentrations of lisinopril on Day 7 were higher in the elderly volunteers than in the young, and still higher in the elderly patients with congestive heart failure. Renal clearance of lisinopril was decreased in the elderly, particularly in the presence of congestive heart failure.
Impaired renal function decreases elimination of lisinopril. This decrease becomes clinically important when the glomerular filtration rate is below 30 mL/min (see Precautions, Impaired Renal Function, and Dosage).
Lisinopril can be removed by dialysis.
Studies in rats indicate that lisinopril crosses the blood-brain barrier poorly.
Indications
Hypertension: ZESTRIL (lisinopril) is indicated in the treatment of essential hypertension and in renovascular hypertension. It may be used alone or concomitantly with thiazide diuretics. A great majority of patients (>80%) with severe hypertension required combination therapy. ZESTRIL has been used concomitantly with beta-blockers and calcium antagonists, but the data on such use are limited.
ZESTRIL should normally be used in those patients in whom treatment with diuretic or beta blocker was found ineffective or has been associated with unacceptable adverse effects. ZESTRIL can also be tried as an initial agent in those patients in whom use of diuretics and/or beta blockers is contraindicated or in patients with medical conditions in which these drugs frequently cause serious adverse effects.
Heart Failure: ZESTRIL is indicated in the management of symptomatic congestive heart failure as adjunctive treatment with diuretics, and where appropriate, digitalis. Treatment with ZESTRIL should be initiated under close medical supervision, usually in a hospital.
High doses of ZESTRIL reduce the risk of the combined outcomes of mortality and hospitalization (see Pharmacology and Dosage).
Treatment Following Acute Myocardial Infarction: ZESTRIL is indicated in the treatment of hemodynamically stable patients as early as within 24 hours following acute myocardial infarction, to improve survival. Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, ASA and betablocker(s).
Therapy with ZESTRIL should be reassessed after 6 weeks. If there is no evidence of symptomatic or asymptomatic left ventricular dysfunction, treatment with ZESTRIL can be stopped.
ZESTRIL should not be used if systolic blood pressure is less than 100 mmHg, if clinically relevant renal failure is present, or if there is a history of bilateral stenosis of the renal arteries (see Precautions, Hypotension Following Acute Myocardial Infarction, Renal Impairment).
General: In using ZESTRIL, attention should be given to the risk of angioedema (see Warnings, Angioedema).
Precautions
Drug Interactions
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 lisinopril. The possibility of symptomatic hypotension with lisinopril can be minimized by discontinuing the diuretic prior to initiation of treatment with lisinopril and/or lowering the initial dose of lisinopril (see Warnings, Hypotension and Dosage).
Hypotension: Patients on Antihypertensive Therapy: When lisinopril is given to patients already treated with other antihypertensive agents, further falls in blood pressure may also occur.
Potassium Supplements, potassium-sparing agents or potassium-containing salt substitutes: Since lisinopril decreases aldosterone production, elevation of serum potassium may occur. Potassium sparing diuretics such as spironolactone, triamterene or amiloride, or potassium supplements should be given only for documented hypokalemia and with caution and with frequent monitoring of serum potassium since they may lead to a significant increase in serum potassium. Potassium-containing salt substitutes should also be used with caution.
Agents Causing Renin Release: The antihypertensive effect of ZESTRIL is augmented by antihypertensive agents that cause renin release (e.g. diuretics).
Agents Affecting Sympathetic Activity: Agents affecting sympathetic activity (e.g., ganglionic blocking agents or adrenergic neuron blocking agents) may be used with caution. Beta-adrenergic blocking drugs add some further antihypertensive effect to lisinopril.
NSAIDS: In some patients with compromised renal function, lisinopril co-administration with nonsteroidal anti-inflammatory drugs (NSAIDs) may produce further renal function deterioration.
Indomethacin may diminish the antihypertensive efficacy of concomitantly administered ZESTRIL.
Lithium Salts: As with other drugs which eliminate sodium, lithium elimination may be reduced. Therefore, the serum lithium levels should be monitored carefully if lithium salts are to be administered.
Antidiabetics: Epidemiological studies have suggested that concomitant administration of ACE inhibitors and antidiabetic medicines (insulins, oral hypoglycaemic 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.
Occupation Hazards
Ability to drive and use machines: dizziness or tiredness may occur during treatment with ZESTRIL.
Children
Safety and effectiveness in children have not been established.
Information to Be Provided to the Patient
Serious Warning and Precautions
ZESTRIL should not be used during pregnancy. Patients should be advised to stop the medication and contact their physician as soon as possible if they discover that they are pregnant while taking ZESTRIL.
Angioedema: Angioedema, including laryngeal edema and, may occur especially following the first dose of lisinopril. Patients should be so advised and told to report immediately any signs or symptoms suggesting angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty in breathing) and to take no more drug until they have consulted with the prescribing physician.
Hypotension: Patients should be cautioned to report light headedness 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 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.
Impaired Liver Function: Patients should be advised to return to the physician if he/she experiences any symptoms possibly related to liver dysfunction. This would include “viral-like symptoms” in the first weeks to months of therapy (such as fever, malaise, muscle pain, rash or adenopathy which are possible indicators of hypersensitivity reactions), or if abdominal pain, nausea or vomiting, loss of appetite, jaundice, itching or any other unexplained symptoms occur during therapy.
Hyperkalemia: Patients should be told not to use salt substitutes containing potassium without consulting their physician.
You are pregnant, breast-feeding or thinking of becoming pregnant? Taking ZESTRIL during pregnancy can cause injury and even death to your baby. This medicine should not be used during pregnancy. If you become pregnant while taking ZESTRIL, stop the medication and report to your doctor as soon as possible. It is possible that ZESTRIL passes into breast milk. You should not breast-feed while taking ZESTRIL.
Note: As with many other drugs, certain advice to patients being treated with ZESTRIL 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.
Supplied
5 mg
Each pink, round, biconvex uncoated tablet, embossed with the number “5” within a heart-shaped symbol on one side and scored on the reverse side, contains: lisinopril 5 mg. Nonmedicinal ingredients: calcium hydrogen phosphate dihydrate, cornstarch, magnesium stearate, mannitol, pregelatinized cornstarch and red iron oxide. Bottles of 100 and calendar packs of 30.
20 mg
Each pink, round, biconvex, uncoated tablet, embossed with the number “20” and “ZESTRIL” within a heart-shaped symbol on one side and blank on the reverse side, contains: lisinopril 20 mg. Nonmedicinal ingredients: calcium hydrogen phosphate dihydrate, cornstarch, magnesium stearate, mannitol, pregelatinized cornstarch and red iron oxide. Bottles of 100 and calendar packs of 30.
Store between 15 and 30°C.
10 mg
Each pink, round, biconvex, uncoated tablet, embossed with the number “10” and “ZESTRIL” within a heart-shaped symbol on one side and blank on the reverse side, contains: lisinopril 10 mg. Nonmedicinal ingredients: calcium hydrogen phosphate dihydrate, cornstarch, magnesium stearate, mannitol, pregelatinized cornstarch and red iron oxide. Bottles of 100 and calendar packs of 30.
Contraindications
ZESTRIL (lisinopril) is contraindicated in patients who:
-
are hypersensitive to any component of this product;
-
have a known allergy to angiotensin converting enzyme inhibitors;
-
have a history of angioneurotic edema relating to previous treatment with an angiotensin-converting enzyme inhibitor;
-
have hereditary or idiopathic angioneurotic edema.
Warnings
Lactation
The presence of concentrations of ACE inhibitor have been reported in human milk. Use of ACE inhibitors is not recommended during breast-feeding.
Race
Angiotensin converting inhibitors cause a higher rate of angioedema in black patients than in non black patients.
The antihypertensive effect of angiotensin converting enzyme inhibitors is generally lower in black patients (usually a low-renin hypertensive population) than in non-black patients.
Pregnancy
ACE inhibitors can cause fetal and neonatal morbidity and mortality when administered to pregnant women. When pregnancy is detected, ZESTRIL should be discontinued as soon as possible.
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, associated with fetal limb contractures, craniofacial deformation, and hypoplastic lung development.
Prematurity, and patent ductus arteriosus and other structural cardiac malformations, as well as neurologic malformations, have also been reported following exposure in the first trimester of pregnancy.
Infants with a history of in utero exposure to ACE inhibitors should be closely observed for hypotension, oliguria, and hyperkalemia. If oliguria occurs, attention should be directed towards support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as a means of reversing hypotension and/or substituting for impaired renal function; however, limited experience with those procedures has not been associated with significant clinical benefit.
Lisinopril has been removed from the neonatal circulation by peritoneal dialysis.
Animal Data: Lisinopril was not teratogenic in mice treated on days 6-15 of gestation with up to 1000 mg/kg/day (625 times the maximum recommended human dose). There was an increase in fetal resorptions at doses down to 100 mg/kg; at doses of 1000 mg/kg, this was prevented by saline supplementation. There was no fetotoxicity or teratogenicity in rats treated with up to 300 mg/kg/day (188 times the maximum recommended dose) of lisinopril at days 6-17 of gestation. In rats receiving lisinopril from day 15 of gestation through day 21 postpartum, there was an increased incidence in pup deaths on days 2-7 postpartum and a lower average body weight of pups on day 21 postpartum. The increase in pup deaths and decrease in pup weight did not occur with maternal saline supplementation.
Lisinopril, at doses up to 1 mg/kg/day, was not teratogenic when given throughout the organogenic period in saline supplemented rabbits. Saline supplementation (physiologic saline in place of tap water) was used to eliminate maternotoxic effects and enable evaluation of the teratogenic potential at the highest possible dosage level. The rabbit has been shown to be extremely sensitive to angiotensin converting enzyme inhibitors (captopril and enalapril) with maternal and fetotoxic effects apparent at or below the recommended therapeutic dosage levels in man.
Fetotoxicity was demonstrated in rabbits by an increased incidence of fetal resorptions at an oral dose of lisinopril of 1 mg/kg/day and by an increased incidence of incomplete ossification at the lowest dose tested (0.1 mg/kg/day). A single intravenous dose of 15 mg/kg of lisinopril administered to pregnant rabbits on gestation days 16, 21 or 26 resulted in 88% to 100% fetal death.
By whole body autoradiography, radioactivity was found in the placenta following administration of labeled lisinopril to pregnant rats, but none was found in the fetuses.
Adverse Effects
Reproductive System and Breast Disorders
Uncommon: impotence.
Metabolism and Nutrition Disorders
Uncommon: hyperkalemia (see Precautions, Hyperkalemia). Rare: hyponatremia. Very rare: hypoglycemia (see Precautions, Diabetic Patients).
Cardiac and Vascular Disorders
Common: orthostatic effects (including hypotension) (see Warnings, Hypotension), syncope (frequency refers to congestive heart failure patient population, frequency in hypertensive patient population is “uncommon”). Uncommon: myocardial infarction or cerebrovascular accident (both possibly secondary to excessive hypotension in high risk patients, see Precautions, Hypotension Following Acute Myocardial Infarction), palpitations, tachycardia.
General Disorders and Administration Site Conditions
Uncommon: fatigue, asthenia.
Hepato-biliary Disorders
Very rare: hepatitis – either hepatocellular or cholestatic, jaundice, hepatic failure. Very rarely it has been reported that in some patients the undesirable development of hepatitis has progressed to hepatic failure. Patients receiving Zestril who develop jaundice or marketed elevation of hepatic enzymes should discontinue Zestril and receive appropriate medical follow-up (see Precautions, Patients with Impaired Liver Function).
Laboratory Test Findings
Serum Electrolytes: Hyperkalemia (see Precautions, Hyperkalemia).
Creatinine, Blood Urea Nitrogen: Increases in blood urea nitrogen and serum creatinine, usually reversible upon discontinuation of therapy, were observed in 1.1 and 1.6% of patients respectively with essential hypertension treated with ZESTRIL alone. Increases were more common in patients receiving concomitant diuretics and in patients with renal artery stenosis (see Precautions, Renal Impairment). In patients with congestive heart failure on 2.5 to 20 mg lisinopril and concomitant diuretic therapy, reversible increases in blood urea nitrogen (14.5%) and serum creatinine (11.2%) were observed in approximately 12.0% of patients. Frequently, these abnormalities resolved when the dosage of the diuretic was decreased.
As shown in the ATLAS trial (see Pharmacology), high dose (up to 35 mg) versus low dose (up to 5 mg) treatment may predispose patients to increased serum creatinine (9.9% versus 7.0%). This event was manageable and rarely led to treatment withdrawal. Therapy discontinuation rates due to increased serum creatinine for high versus low dose were 0.3% versus 0.4%, respectively.
Hematology: Decreases in hemoglobin and hematocrit (mean decreases of approximately 0.9 g % and 0.6 vol %, respectively) occurred frequently in patients treated with ZESTRIL but were rarely of clinical importance in patients without some other cause of anemia. Rarely, hemolytic anemia has been reported.
Agranulocytosis and bone marrow depression, manifested as anemia, cytopenia or leukopenia, have been caused by angiotensin converting enzyme inhibitors, including lisinopril. Several cases of agranulocytosis and neutropenia have been reported in which a causal relationship to lisinopril cannot be excluded (see Warnings, Neutropenia/Agranulocytosis).
Hepatic: Elevations of liver enzymes and/or serum bilirubin have occurred (see Precautions, Patients with Impaired Liver Function).
Discontinuations: Overall, 1.0% of patients discontinued therapy due to laboratory adverse experiences, principally elevations in blood urea nitrogen (0.8%), serum creatinine (0.1%) and serum potassium (0.1%).
Renal and Urinary Disorders
Common: renal dysfunction. Rare: uremia, acute renal failure. Very rare: oliguria/anuria (see Precautions, Renal Impairment).
Skin and Subcutaneous Tissue Disorders
Uncommon: rash, pruritis, hypersensitivity/angioneurotic edema: angioneurotic edema of the face, extremities, lips, tongue, glottis, and/or larynx (see Warnings, Hypersensitivity/Angioedema). Rare: urticaria, alopecia, psoriasis. Very rare: diaphoresis, pemphigus, toxic epidermal necrolysis, Steven-Johnson Syndrome, erythema multiforme.
A symptom complex has been reported which may include one or more of the following: fever, vasculitis, myalgia, arthralgia/arthritis, a positive antinuclear antibodies (ANA), elevated red blood cell sedimentation rate (ESR), oesinophilia and leukocytosis. Rash, photosensitivity or other dermatological manifestations may occur.
ZESTRIL
Adverse Events—Treatment Following Acute Myocardial InfarctionEvent Control
n=4729Lisinopril
n=4713Lisinopril
+ GTN
n=4722GTN
Alone
n=4731Persistent Hypertension 3.6 8.8 9.3 3.9 Shock 2.5 2.8 2.2 1.9 Renal Dysfunction 1.1 2.4 2.4 1.1 Stroke 0.6 0.6 0.9 0.8 Re-infarction 2.2 2.2 2.2 1.9 Hemorrhagic Events 1.2 1.3 1.1 0.9 Post-infarction Angina 13.2 13.9 12.3 11.8 Ventricular Fibrillation 3.1 2.5 2.4 2.2 Sustained Ventricular Tachycardia 2.5 2.1 1.8 2.3 Atrial Flutter or Fibrillation 6.4 6.3 5.3 5.7 Complete Atrioventricular Block 2.4 2.9 2.5 2.1 Asystole 1.2 1.2 1.3 1.2 Intraventricular Septal Rupture 0.3 0.4 0.2 0.2 Papillary Muscle Rupture 0.3 0.4 0.5 0.4 Late CHF (>4 days) 4.5 4.5 4.2 4.2
Post-Marketing Experience
The following undesirable effects have been observed and reported during treatment with ZESTRIL with the following frequencies: Very common (≥10%), common (≥1%, <10%), uncommon (≥0.1%, <1%), rare (≥0.01%, <0.1%), very rare (<0.01%) including isolated reports.
Blood and Lymphatic System Disorders
Very rare: bone marrow depression, anemia thrombocytopenia, leucopenia, agranulocytosis, hemolytic anemia (see Warnings, Neutropenia/Agranulocytosis).
Respiratory Thoracic and Mediastinal Disorders
Common: cough. Uncommon: rhinitis. Very rare: bronchospasm, sinusitis.
Investigations
Uncommon: increases in blood urea, increases in serum creatinine (see Precautions, Renal Impairment), increases in liver enzymes (see Precautions, Patients with Impaired Liver Function). Rare: decreases in hemoglobin, decreases in hematocrit, increases in serum bilirubin (see Precautions, Patients with Impaired Liver Function).
Gastrointestinal Disorders
Common: diarrhoea, vomiting. Uncommon: nausea, abdominal pain and indigestion. Rare: dry mouth. Very rare: pancreatitis, intestinal angioedema (see Warnings, Hypersensitivity/Angioedema and Adverse Effects, Angioedema).
Nervous System and Psychiatric Disorders
Common: dizziness, headache. Uncommon: mood alterations (including depressive symptoms), paraesthesia, vertigo, taste disturbance, sleep disturbances. Rare: mental confusions.
Overdose
Symptoms
Overdose symptoms include severe hypotension, electrolyte disturbances, and renal failure.
Treatment
Overdosed patients should be kept under very close observation. Therapeutic measures depend on the nature and severity of symptoms. Measures to prevent absorption and methods to speed elimination should be employed. If severe hypotension occurs, place the patient in the shock position and infuse intravenous normal saline immediately. Vasopressors including angiotensin II may be considered if fluid replacement is inadequate or contraindicated. Circulating lisinopril may be removed by hemodialysis. Avoid high-flux polyacrylonitrile dialysis membranes (see Precautions, Anaphylactoid Reactions during membrane exposure). Serum electrolytes and creatinine should be monitored frequently.
Dosage
Since absorption of ZESTRIL tablets (lisinopril) is not affected by food, the tablets may be administered before, during or after meals. ZESTRIL should be administered in a single daily dose. ZESTRIL should be taken at the same time each day.
Dosage must be individualized and should be adjusted according to blood pressure response.
Essential Hypertension: In patients with essential hypertension, not on diuretic therapy, the usual recommended starting dose is 10 mg once a day. The usual dosage range is 10 to 40 mg per day, administered in a single daily dose. The antihypertensive effect may diminish toward the end of the dosing interval regardless of the administered dose, but most commonly with a dose of 10 mg daily. This can be evaluated by measuring blood pressure just prior to dosing to determine whether satisfactory control is being maintained for 24 hours. If it is not, an increase in dose should be considered. The maximum dose used in long-term controlled clinical trials was 80 mg/day. If blood pressure is not controlled with ZESTRIL alone, a low dose of diuretic may be added. Hydrochlorothiazide 12.5 mg has been shown to provide an additive effect. After the addition of diuretic, it may be possible to reduce the dose of ZESTRIL.
Diuretic Treated Patients: In hypertensive patients who are currently being treated with a diuretic, symptomatic hypotension may occur occasionally following the initial dose of ZESTRIL. The diuretic should be discontinued, if possible, for two to three days before beginning therapy with ZESTRIL to reduce the likelihood of hypotension (see Warnings). The dosage of ZESTRIL should be adjusted according to blood pressure response. If the patient's blood pressure is not controlled with ZESTRIL alone, diuretic therapy may be resumed as described above.
If the diuretic cannot be discontinued, an initial dose of 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, Hypotension and Precautions, Drug Interactions).
A lower starting dose is required in the presence of renal impairment, in patients in whom diuretic therapy cannot be discontinued, patients who are volume and/or salt-depleted for any reason, and in patients with renovascular hypertension.
Dosage Adjustment in Renal Impairment: Dosage in patients with renal impairment should be based on creatinine clearance as outlined in Table 3.
Table 3: ZESTRIL
Dosage Adjustment in Renal Impairment
a. Dosage and/or frequency of administration should be adjusted depending on the blood pressure response.Creatinine Clearance Starting Dose
mg/daymL/s (mL/min) 0.5–1.17 31–70 5–10 0.17–0.5 10–30 2.5–5 <0.17
(including patients on dialysis)<10
(including patients on dialysis)2.5a
The dosage may be titrated upward until blood pressure is controlled or to a maximum of 40 mg daily.
Anaphylactoid reactions have been reported in patients dialysed with high-flux membranes (e.g.:polyacrylonitrile [PAN]and during low-density lipoproteins (LDL) apheresis with dextran suphate) and treated concomitantly with an ACE inhibitor (see Precautions, Anaphylactoid Reactions during membrane exposure).
Geriatrics: In general, blood pressure response and adverse experiences were similar in younger and older patients given similar doses of ZESTRIL. Pharmacokinetic studies, however, indicate that maximum blood levels and area under the plasma concentration time curve (AUC) are doubled in older patients so that dosage adjustments should be made with particular caution.
Renovascular Hypertension: Some patients with renovascular hypertension, especially those with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, may develop an exaggerated response to the first dose of ZESTRIL. In these patients, treatment should be started at low doses (2.5 or 5 mg), under close medical supervision. Thereafter, the dosage may be adjusted according to the blood pressure response. Doses should be carefully titrated.
Congestive Heart Failure: ZESTRIL is to be used in conjunction with diuretics, and where appropriate digitalis. Therapy must be initiated under close medical supervision, usually in a hospital. Blood pressure and renal function should be monitored, both before and during treatment with ZESTRIL, because severe hypotension and, more rarely, consequent renal failure have been reported (see Warnings, Hypotension and Precautions, Renal Impairment).
Initiation of therapy requires consideration of recent diuretic therapy and the possibility of severe salt/volume depletion. If possible, the dose of diuretic should be reduced before beginning treatment.
The recommended initial dose is 2.5 mg per day. The ZESTRIL dose should be increased: by increments of no greater than 10 mg; at intervals of no less than 2 weeks, up to a maximum of 35 mg once daily. Dose adjustment should be based on the individual patient's tolerance and clinical response.
Treatment Following Acute Myocardial Infarction: Treatment with ZESTRIL may be started as early as within 24 hours following the onset of symptoms in hemodynamically stable patients. Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, ASA and beta-blocker(s) (see Indications, Treatment Following Acute Myocardial Infarction).
The first dose of ZESTRIL is 5 mg given orally, followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg once daily thereafter.
Patients with a low systolic blood pressure (between 100 and 120 mmHg) when treatment is started or during the first 3 days after the infarct should be given a lower dose—2.5 mg orally. Treatment with ZESTRIL must not be initiated in patients who are at risk of serious hemodynamic deterioration (see Precautions, Hypotension Following Acute Myocardial Infarction). After three days, if hypotension occurs (systolic blood pressure less than or equal to 100 mmHg), a daily maintenance dose of 5 mg may be given with temporary reductions to 2.5 mg if needed. If prolonged hypotension occurs (systolic blood pressure less than 90 mmHg for more than 1 hour), ZESTRIL should be withdrawn.
Renal function should be assessed before and during therapy with ZESTRIL (see Precautions, Renal Impairment).
Dosing should normally continue for six weeks. At that time, patients with signs or symptoms of heart failure should continue with ZESTRIL (see Dosage, Congestive Heart Failure).
ZESTRIL is compatible with intravenous or transdermal glyceryl trinitrate.
