Zestoretic
Zestoretic Medication Information:
Zestoretic medication comes in several different strengths; click on the strength you need to view prices from pharmacies competing to earn your business.
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Zestoretic 10mg/12.5mg
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Zestoretic 20mg/25mg
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Zestoretic 20mg/12.5mg
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Pharmacology
Pharmacokinetics
Lisinopril: Following oral administration of lisinopril, peak serum concentrations occur within about 7 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 to plasma 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.
Upon multiple dosing, lisinopril exhibits an effective half-life of accumulation of 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. Maximum serum concentrations of lisinopril on Day 7 were higher in the elderly volunteers than in the young.
Impaired renal function decreases elimination of lisinopril. This decrease becomes clinically important when the glomerular filtration rate is below 30 mL/min (see Precautions, Renal Impairment and Dosage).
Lisinopril can be removed by dialysis.
Studies in rats indicate that lisinopril crosses the blood-brain barrier poorly.
Hydrochlorothiazide: Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. The plasma half-life is 5.6-14.8 hours when the plasma levels can be followed for at least 24 hours. At least 61% of the oral dose is eliminated unchanged within 24 hours. Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
Onset of the diuretic action following oral administration occurs in 2 hours and the peak action in about 4 hours. Diuretic activity lasts about 6 to 12 hours.
Lisinopril-Hydrochlorothiazide: Concomitant administration of lisinopril and hydrochlorothiazide has little, or no effect on the bioavailability of either drug. The combination tablet is bioequivalent to concomitant administration of the separate entities.
Pharmacodynamics
Lisinopril: Administration of lisinopril to patients with hypertension results in a reduction of both supine and standing blood pressure. Abrupt withdrawal of lisinopril has not been associated with a rapid increase in blood pressure. In most patients studied, after oral administration of an individual dose of lisinopril, the onset of antihypertensive activity is seen at one hour with peak reduction of blood pressure achieved by 6 hours. Although an antihypertensive effect was observed 24 hours after dosing with recommended single daily doses, the effect was more consistent and the mean effect was considerably larger in some studies with doses of 20 mg or more than with lower doses. However, at all doses studied, the mean antihypertensive effect was substantially smaller 24 hours after dosing than it was 6 hours after dosing. On occasion, achievement of optimal blood pressure reduction may require 2 to 4 weeks of therapy.
In hemodynamic studies in patients with essential hypertension, blood pressure reduction was accompanied by a reduction in peripheral arterial resistance with little or no change in cardiac output and in heart rate. In a study in nine hypertensive patients, following administration of lisinopril, there was an increase in mean renal blood flow that was not significant. Data from several small studies are inconsistent with respect to the effect of lisinopril on glomerular filtration rate in hypertensive patients with normal renal function, but suggest that changes, if any, are not large.
Indications
ZESTORETIC (lisinopril and hydrochlorothiazide) is indicated for the treatment of essential hypertension in patients for whom combination therapy is appropriate.
In using ZESTORETIC, consideration should be given to the risk of angioedema (see Warnings, Angioedema).
Lisinopril should normally be used in those patients in whom treatment with diuretic or betablocker was found ineffective or has been associated with unacceptable adverse effects.
ZESTORETIC is not indicated for initial therapy. Patients in whom lisinopril and diuretic are initiated simultaneously can develop symptomatic hypotension (see Precautions, Drug Interactions).
Patients should be titrated on the individual drugs. If the fixed combination represents the dosage determined by this titration, the use of ZESTORETIC may be more convenient in the management of patients. If during maintenance therapy dosage adjustment is necessary, it is advisable to use individual drugs.
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 hypotensive effects with lisinopril can be minimized by either discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with lisinopril (see Warnings, 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 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. Salt substitutes which contain potassium should also be used with caution.
Agents Causing Renin Release: The antihypertensive effect of ZESTORETIC 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.
Lithium: Lithium generally should not be given with diuretics or ACE inhibitors. Diuretic agents and ACE inhibitors reduce the renal clearance of lithium and add a high risk of lithium toxicity.
d-tubocurarine: Thiazide drugs may increase the responsiveness to tubocurarine.
Insulin and Oral Hypoglycemic Agents: Insulin and oral hypoglycemic agents requirements in diabetic patients may be increased, decreased or unchanged. Previously latent diabetes mellitus may become manifest during thiazide administration (see Precautions, Metabolism).
Alcohol, Barbiturates, Or Narcotics: Potentiation of orthostatic hypotension may occur.
Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia may occur.
Pressor Amines (e.g. norepinephrine): Possible decreased response to pressor amines but not sufficient to preclude their use.
Non Steroidal Anti-inflammatory Drugs: In some patients, the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when ZESTORETIC and non-steroidal antiinflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.
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 lisinopril and hydrochlorothiazide.
Geriatrics
In general, blood pressure response and adverse experiences were similar in younger and older patients given similar doses of lisinopril. 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.
Occupational Hazards
Ability to drive and use machines: Dizziness or tiredness may occur during treatment with ZESTORETIC.
Children
ZESTORETIC has not been studied in children and, therefore, use in this age group is not recommended.
Information to Be Provided to the Patient
Serious Warning and Precautions
ZESTORETIC 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 ZESTORETIC.
Angioedema: Angioedema, including laryngeal, may occur during treatment with ZESTORETIC. 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 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 diarrhoea 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.
You are pregnant, breast-feeding or thinking of becoming pregnant? Taking ZESTORETIC 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 ZESTORETIC, stop the medication and report to your doctor as soon as possible. It is possible that ZESTORETIC passes into breast milk. You should not breast-feed while taking ZESTORETIC.
Note: As with many other drugs, certain advice to patients being treated with ZESTORETIC 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 events.
Supplied
20/12.5
Each white, round, biconvex tablet, with “Zestoretic” intagliated on one side and blank on the other side, contains: lisinopril 20 mg and hydrochlorothiazide 12.5 mg. Nonmedicinal ingredients: calcium hydrogen phosphate dihydrate, corn starch, magnesium stearate, mannitol, pregelatinized starch. Bottles of 100. Calendar packs of 30.
10/12.5
Each peach, round, biconvex tablet, with “Zt” over “10” intagliated on one side and blank on the other side, contains: lisinopril 10 mg and hydrochlorothiazide 12.5 mg. Nonmedicinal ingredients: calcium hydrogen phosphate dihydrate, corn starch, magnesium stearate, mannitol, pregelatinized starch, red iron oxide and yellow iron oxide. Bottles of 100. Calendar packs of 30.
20/25
Each peach, round, biconvex tablet, with “Zestoretic” intagliated on one side and blank on the other side, contains: lisinopril 20 mg and hydrochlorothiazide 25 mg. Nonmedicinal ingredients: calcium hydrogen phosphate dihydrate, corn starch, magnesium stearate, mannitol, pregelatinized starch, red iron oxide and yellow iron oxide. Bottles of 100. Calendar packs of 30.
Store at controlled room temperature 15 to 30°C. Keep container tightly closed. Protect from light.
Contraindications
ZESTORETIC (lisinopril and hydrochlorothiazide) is contraindicated in patients who:
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are hypersensitive to any component of this product;
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have a known allergy to angiotensin converting enzyme inhibitors;
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have a history of angioneurotic edema relating to previous treatment with an angiotensin converting enzyme inhibitor;
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have hereditary or idiopathic angioneurotic edema, and because of the hydrochlorothiazide component, in patients who have anuria;
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hypersensitivity to other sulfonamide-derived drugs.
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, ZESTORETIC 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 increase 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 labelled lisinopril to pregnant rats, but none was found in the fetuses.
Adverse Effects
Reproductive System and Breast Disorders
Common: impotence.
Abnormal Laboratory Findings
Hypokalemia, Hyperkalemia: (See Precautions, Hyperkalemia, and Drug Interactions).
Creatinine, Blood Urea Nitrogen: Minor increases in blood urea nitrogen (3.8%) and serum creatinine (4.2%) were observed in patients with essential hypertension treated with ZESTORETIC. More marked increases have also been reported and were more likely to occur in patients with bilateral renal artery stenosis (see Precautions, Renal Impairment).
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 lisinopril alone.
Serum Uric Acid, Glucose, Magnesium, Cholesterol, Triglycerides and Calcium: (See Precautions, Metabolism).
Hemoglobin and Hematocrit: Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.5 g percent and 1.5 vol percent, respectively) occurred frequently in hypertensive patients treated with ZESTORETIC but were rarely of clinical importance unless another cause of anemia coexisted. In clinical trials, 0.4% of patients discontinued therapy due to 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).
Metabolism and Nutrition Disorders
Uncommon: gout. Rare: hyperkalemia (see Precautions, Hyperkalemia), hypokalemia, hyperuricemia, hyperglycemia (see Precautions, Metabolism).
Cardiac and Vascular Disorders
Common: orthostatic effects (including hypotension), syncope. Uncommon: palpitations.
General Disorders and Administration Site Conditions
Common: fatigue, asthenia. Uncommon: chest discomfort.
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 ZESTORETIC who develop jaundice or marked elevation of hepatic enzymes should discontinue ZESTORETIC and receive appropriate medical follow up (see Warnings, Patients with Impaired Liver Function).
Respiratory, Thoracic and Mediastinal Disorders
Common: cough (see Precautions, Cough).
Skin and Subcutaneous Tissue Disorders
Common: rash. Uncommon: hypersensitivity/angioneurotic oedema: angioneurotic oedema of the face, extremities, lips, tongue, glottis and/or larynx (see Warnings, Angioedema).
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), eosinophilia and leucocytosis, rash, photosensitivity or other dermatological manifestation may occur.
Musculoskeletal, Connective Tissue And Bone Disorders
Common: muscle cramps. Rare: muscle weakness.
Post-Marketing Experience
The following undesirable effects have been observed and reported during treatment with ZESTORETIC 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
Rare: anaemia. Very rare: agranulocytosis, bone marrow depression, thrombocytopenia, leucopenia, hemolytic anaemia (see Warnings, Neutropenia/Agranulocytosis).
ZESTORETIC
Incidence of Adverse Reactions Occurring in Patients Treated with ZESTORETIC in Controlled Clinical Trials
a. See ZESTORETIC (Marketing Experience Only).Lisinopril
2633 Patients
(%)Lisinopril Plus
Hydrochlorothiazide
930 Patients
(%)Cardiovascular Hypotension 0.8 1.9 Orthostatic Effects 0.9 3.2 Chest Pain 1.1 1.0 Syncope 0.2 0.8 Angina 0.3 0.1 Edema 0.6 0.1 Palpitation 0.8 0.9 Rhythm Disturbances 0.5 0.1 Chest Discomfort — 0.6 Gastrointestinal Diarrhea 1.8 2.5 Nausea 1.9 2.2 Vomiting 1.1 1.4 Dyspepsia 0.5 1.3 Anorexia 0.4 0.2 Constipation 0.2 0.3 Flatulence 0.3 0.2 Abdominal Pain 1.4 0.9 Dry mouth 0.5 0.2 Nervous System Dizziness 4.4 7.5 Headache 5.6 5.2 Paresthesia 0.5 1.5 Depression 0.7 0.5 Somnolence 0.8 0.4 Insomnia 0.3 0.2 Vertigo 0.2 0.9 Respiratory Cough 3.0 3.9 Dyspnea 0.4 0.4 Upper Respiratory Infection 2.1 2.2 Dermatologic Rash 1.0 1.2 Pruritus 0.5 0.4 Flushing 0.3 0.8 Angioedema 0.1 —a Musculoskeletal Muscle Cramps 0.5 2.0 Back Pain 0.5 0.8 Shoulder Pain 0.2 0.5 Other Fatigue — 3.7 Asthenia 2.7 1.8 Decreased Libido 0.2 1.0 Fever 0.3 0.5 Impotence 0.7 1.2 Gout 0.2 0.2
Investigations
Common: increases in blood urea, increases in serum creatinine (see Precautions, Renal Impairment), increases in liver enzymes (see Warnings, Patients with Impaired Liver Function), decreases in haemoglobin. Uncommon: decreases in haematocrit. Rare: increases in serum bilirubin (see Warnings, Patients with Impaired Liver Function).
Lisinopril: Myocardial infarction or cerebrovascular accident possibly secondary to excessive hypotension in high risk patients, tachycardia, abdominal pain and ingestion, mood alterations, mental confusion and vertigo have occurred; as with other angiotensin converting enzyme inhibitors, taste disturbance and sleep disturbance have been reported; bronchospasm, rhinitis, sinusitis, alopecia, urticaria, diapheresis, pruritis, psoriasis and severe skin disorders (including pemphigus, toxic epidermal necrolysis, Steven-Johnson Syndrome and erythema multiforme), have been reported; hyponatraemia, uraemia, oliguria/anuria, renal dysfunction, acute renal failure, pancreatitis; rarely, haemolytic anaemia has been reported.
Hydrochlorothiazide: anorexia, gastric irritation, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis, sialoadenitis, vertigo, xanthopsia, leucopenia, agranulocytosis, thrombocytopenia, aplastic anemia, haemolytic anaemia, purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis) (cutaneaous vasculitis), fever, respiratory distress including pneumonitis and pulmonary oedema, anaphylactic reactions, hyperglycaemia, glycosuria, hyperuricemia, electrolyte imbalance including hyponatremia, muscle spasm, restlessness, transient blurred vision, renal failure, renal dysfunction and interstitial nephritis.
Gastrointestinal Disorders
Common: diarrhoea, nausea, vomiting. Uncommon: dry mouth. Rare: pancreatitis. Very rare: intestinal angioedema.
Nervous System and Psychiatric Disorders
Common: dizziness, headache, paraesthesia. Uncommon: depressive symptoms.
Overdose
Symptoms
No specific information is available on the treatment of overdosage with ZESTORETIC (lisinopril and hydrochlorothiazide). Treatment is symptomatic and supportive. Therapy with ZESTORETIC should be discontinued and the patient observed closely. Suggested measures include induction of emesis and/or gastric lavage, if ingestion is recent, and correction of dehydration, electrolyte imbalance and hypotension by established procedures.
Lisinopril: Overdose symptoms include severe hypotension, electrolyte disturbances and renal failure. 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.
Hydrochlorothiazide: The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.
Treatment
See Symptoms.
Dosage
Essential hypertension: Dosage must be individualized. The fixed combination is not for initial therapy. The dose of ZESTORETIC (lisinopril and hydrochlorothiazide) should be determined by the titration of the individual components. ZESTORETIC should be taken at the same time each day.
Once the patient has been successfully titrated with the individual components as described below, either one ZESTORETIC 10/12.5 mg or one or two 20/12.5 mg or 20/25 mg tablets once daily may be substituted if the titrated doses are the same as those in the fixed combination. (See Indications and Warnings.)
Patients usually do not require doses in excess of 50 mg of hydrochlorothiazide daily, particularly when combined with antihypertensive agents.
For lisinopril monotherapy the recommended initial dose in patients not on diuretics is 10 mg of lisinopril once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range of lisinopril is 10 to 40 mg 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 lisinopril alone, a low dose of a diuretic may be added. Hydrochlorothiazide 12.5 mg has been shown to provide an additive effect. After the addition of a diuretic, it may be possible to reduce the dose of lisinopril.
Diuretic Treated Patients: In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally may occur following the initial dose of lisinopril. The diuretic should if possible, be discontinued for two to three days before beginning therapy with lisinopril to reduce the likelihood of hypotension (see Warnings, Hypotension). The dosage of lisinopril should be adjusted according to blood pressure response.
If the patient's blood pressure is not controlled with lisinopril alone, diuretic therapy may be resumed as described above.
If the diuretic cannot be discontinued, an initial dose of 5 mg of lisinopril alone should be administered and the patient remain 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).
Dosage Adjustment in Renal Impairment: In patients with creatinine clearance greater than 30 mL/min the usual dose titration of the individual components is required.
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 sulphate and treated concomitantly with an ACE inhibitor. (See Precautions, Anaphylactoid Reactions during membrane exposure.)
For patients with creatinine clearance between 10 and 30 mL/min the starting dose of lisinopril is 2.5-5.0 mg/day. The dosage may then be titrated upward until blood pressure is controlled or to a maximum of 40 mg daily.
When concomitant diuretic therapy is required in patients with severe renal impairment (creatinine clearance <10 mL/min), a loop diuretic, rather than a thiazide diuretic is preferred for use with lisinopril. Therefore, for patients with severe renal dysfunction the lisinoprilhydrochlorothiazide combination tablet is not recommended.
