Disclaimer:
Medidex is not a provider of medical services and all information is provided for the convenience of the user. No medical decisions should be made based on the information provided on this website without first consulting a licensed healthcare provider.This website is intended for persons 18 years or older. No person under 18 should consult this website without the permission of a parent or guardian.
Perindopril Erbumine
Overview
What is Perindopril Erbumine?
Perindopril erbumine tablets are the tert-butylamine salt of perindopril, the ethyl ester of a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor. Perindopril erbumine is chemically described as (2S,3αS,7αS)-1-[(S)-N-[(S)-1-Carboxy-butyl]alanyl]hexahydro-2-indolinecarboxylic acid, 1-ethyl ester, compound with tert-butylamine (1:1). Its molecular formula is CHNOCHN. Its structural formula is:
Perindopril erbumine is a white, crystalline powder with a molecular weight of 368.47 (free acid) or 441.61 (salt form). It is freely soluble in water (60% w/w), alcohol and chloroform.
Perindopril is the free acid form of perindopril erbumine, is a pro-drug and metabolized by hydrolysis of the ester group to form perindoprilat, the biologically active metabolite.
Perindopril erbumine tablets are available in 2 mg, 4 mg and 8 mg strengths for oral administration. In addition to perindopril erbumine, each tablet contains the following inactive ingredients: hydrophobic colloidal silica, lactose monohydrate, magnesium stearate and microcrystalline cellulose.
What does Perindopril Erbumine look like?
What are the available doses of Perindopril Erbumine?
Sorry No records found.
What should I talk to my health care provider before I take Perindopril Erbumine?
Sorry No records found
How should I use Perindopril Erbumine?
Stable Coronary Artery Disease
Perindopril erbumine tablets are indicated in patients with stable coronary artery disease to reduce the risk of cardiovascular mortality or non-fatal myocardial infarction. Perindopril erbumine tablets can be used with conventional treatment for management of coronary artery disease, such as antiplatelet, antihypertensive or lipid-lowering therapy.
Hypertension
Perindopril erbumine tablets are indicated for the treatment of patients with essential hypertension. Perindopril erbumine tablets may be used alone or given with other classes of antihypertensives, especially thiazide diuretics.
When using perindopril erbumine tablets, 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. Available data are insufficient to determine whether perindopril erbumine tablets has a similar potential. (See .)
In considering use of perindopril erbumine tablets, it should be noted that in controlled trials ACE inhibitors have an effect on blood pressure that is less in black patients than in nonblacks. In addition, it should be noted that black patients receiving ACE inhibitor monotherapy have been reported to have a higher incidence of angioedema compared to nonblacks. (See .)
Stable Coronary Artery Disease
In patients with stable coronary artery disease, perindopril erbumine tablets should be given at an initial dose of 4 mg once daily for 2 weeks, and then increased as tolerated, to a maintenance dose of 8 mg once daily. In elderly patients (>70 yrs), perindopril erbumine tablets should be given as a 2 mg dose once daily in the first week, followed by 4 mg once daily in the second week and 8 mg once daily for maintenance dose if tolerated.
Hypertension
Use in Uncomplicated Hypertensive Patients:
If the diuretic cannot be discontinued, an initial dose of 2 to 4 mg daily in one or in two divided doses should be used with careful medical supervision for several hours and until blood pressure has stabilized. The dosage should then be titrated as described above. (See and .)
After the first dose of perindopril erbumine tablets, the patient should be followed closely for the first two weeks of treatment and whenever the dose of perindopril erbumine tablets and/or diuretics is increased (See and , .) In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally can occur following the initial dose of perindopril erbumine tablets. To reduce the likelihood of hypotension, the dose of diuretic, if possible, can be adjusted which may diminish the likelihood of hypotension. The appearance of hypotension after the initial dose of perindopril erbumine tablets does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension.
Dose Adjustment in Renal Impairment
Kinetic data indicate that perindoprilat elimination is decreased in renally impaired patients, with a marked increase in accumulation when creatinine clearance drops below 30 mL/min. In such patients (creatinine clearance <30 mL/min), safety and efficacy of perindopril erbumine tablets have not been established. For patients with lesser degrees of impairment (creatinine clearance above 30 mL/min), the initial dosage should be 2 mg/day and dosage should not exceed 8 mg/day due to limited clinical experience. During dialysis, perindopril is removed with the same clearance as in patients with normal renal function.
What interacts with Perindopril Erbumine?
Perindopril erbumine tablets are contraindicated in patients known to be hypersensitive to this product or to any other ACE inhibitor. Perindopril erbumine tablets are also contraindicated in patients with a history of angioedema related to previous treatment with an ACE inhibitor.
What are the warnings of Perindopril Erbumine?
As with other agents that have anticonvulsant activity, when diazepam is used
as an adjunct in treating convulsive disorders, the possibility of an increase
in the frequency and/or severity of grand mal seizures may require an increase
in the dosage of standard anticonvulsant medication. Abrupt withdrawal of
diazepam in such cases may also be associated with a temporary increase in the
frequency and/or severity of seizures.
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 perindopril erbumine tablets) may be subject to a variety of adverse reactions, some of them serious.
Head and Neck Angioedema:
Angioedema involving the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with ACE inhibitors, including perindopril erbumine tablets (0.1% of patients treated with perindopril erbumine tablets in U.S. clinical trials). In such cases, perindopril erbumine tablets should be promptly discontinued and the patient carefully observed until the swelling disappears. 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 involvement of the tongue, glottis or larynx may be fatal due to airway obstruction. Appropriate therapy, such as subcutaneous epinephrine solution 1:1000 (0.3 to 0.5 mL), should be promptly administered. Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor.
Intestinal Angioedema:
Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.
Anaphylactoid Reactions During Desensitization:
Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge.
Anaphylactoid Reactions During Membrane Exposure:
Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.
Hypotension:
Like other ACE inhibitors, perindopril erbumine tablets can cause symptomatic hypotension. Perindopril erbumine tablets have been associated with hypotension in 0.3% of uncomplicated hypertensive patients in U.S. placebo-controlled trials. Symptoms related to orthostatic hypotension were reported in another 0.8% of patients.
Symptomatic hypotension associated with the use of ACE inhibitors is more likely to occur in patients who have been volume and/or salt-depleted, as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea or vomiting. Volume and/or salt depletion should be corrected before initiating therapy with perindopril erbumine tablets. (See .)
In patients with congestive heart failure, with or without associated renal insufficiency, ACE inhibitors may cause excessive hypotension, and may be associated with oliguria or azotemia, and rarely with acute renal failure and death. In patients with ischemic heart disease or cerebrovascular disease such an excessive fall in blood pressure could result in a myocardial infarction or a cerebrovascular accident.
In patients at risk of excessive hypotension, perindopril erbumine tablets therapy should be started under very close medical supervision. Patients should be followed closely for the first two weeks of treatment and whenever the dose of perindopril erbumine tablets and/or diuretic is increased.
If excessive hypotension occurs, the patient should be placed immediately in a supine position and, if necessary, treated with an intravenous infusion of physiological saline. Perindopril erbumine tablets treatment can usually be continued following restoration of volume and blood pressure.
Neutropenia/Agranulocytosis:
Another ACE 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 patients with a collagen vascular disease such as systemic lupus erythematosus or scleroderma. Available data from clinical trials of perindopril erbumine tablets are insufficient to show whether perindopril erbumine tablets causes agranulocytosis at similar rates.
Fetal/Neonatal Morbidity and Mortality:
ACE inhibitors can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature. When pregnancy is detected, ACE inhibitors should be discontinued as soon as possible.
The use of ACE inhibitors during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation and hypoplastic lung development.
Prematurity, intrauterine growth retardation, patent ductus arteriosus, and other structural cardiac malformations, as well as neurological malformations, have been reported following exposure to ACE inhibitors during the first trimester of pregnancy.
When patients become pregnant, physicians should make every effort to discontinue the use of perindopril erbumine tablets as soon as possible. Rarely (probably less often than once in every thousand pregnancies), no alternative to ACE inhibitors will be found. In these rare cases, the mothers should be apprised of the potential hazards to their fetuses, and serial ultrasound examinations should be performed to assess the intra-amniotic environment.
If oligohydramnios is observed, perindopril erbumine tablets should be discontinued unless it is considered life-saving for the mother. Contraction stress testing (CST), a non-stress test (NST) or biophysical profiling (BPP) may be appropriate, depending upon the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.
Infants with histories of exposure to ACE inhibitors should be closely observed for hypotension, oliguria and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function. Perindopril, which crosses the placenta, can theoretically be removed from the neonatal circulation by these means, but limited experience has not shown that such removal is central to the treatment of these infants.
No teratogenic effects of perindopril were seen in studies of pregnant rats, mice, rabbits and cynomolgus monkeys. On a mg/m basis, the doses used in these studies were 6 times (in mice), 670 times (in rats), 50 times (in rabbits) and 17 times (in monkeys) the maximum recommended human dose (assuming a 50 kg adult). On a mg/kg basis, these multiples are 60 times (in mice), 3,750 times (in rats), 150 times (in rabbits) and 50 times (in monkeys) the maximum recommended human dose.
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.
What are the precautions of Perindopril Erbumine?
General:
Array
Impaired Renal Function:
Array
Hypertensive Patients with Congestive Heart Failure:
Array
Hypertensive Patients with Renal Artery Stenosis:
Some hypertensive patients without apparent pre-existing renal vascular disease have developed increases in blood urea nitrogen and serum creatinine, usually minor and transient. These increases are more likely to occur in patients treated concomitantly with a diuretic and in patients with pre-existing renal impairment. Reduction of dosages of perindopril erbumine tablets, the diuretic or both may be required. In some cases, discontinuation of either or both drugs may be necessary.
Evaluation of hypertensive patients should always include an assessment of renal function. (See .)
Array
Cough:
Array
Surgery/Anesthesia:
Information for Patients:
Array
Angioedema:
Array
Symptomatic Hypotension:
All patients should be cautioned that inadequate fluid intake or excessive perspiration, diarrhea or vomiting can lead to an excessive fall in blood pressure in association with ACE inhibitor therapy.
Array
Hyperkalemia:
e.g.
Array
Pregnancy:
Drug Interactions:
The rate and extent of perindopril absorption and elimination are not affected by concomitant diuretics. The bioavailability of perindoprilat was reduced by diuretics, however, and this was associated with a decrease in plasma ACE inhibition.
Array
Potassium Supplements and Potassium-Sparing Diuretics:
Array
Lithium:
Array
Gold:
Array
Digoxin:
Array
Gentamicin:
Array
Food Interaction:
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Array
Carcinogenesis:
in vitro
in vivo
Saccharomyces cerevisiae
Array
Impairment of Fertility:
Pregnancy:
Pregnancy Categories D. (See .)
Nursing Mothers:
Milk of lactating rats contained radioactivity following administration C-perindopril. It is not known whether perindopril is secreted in human milk. Because many drugs are secreted in human milk, caution should be exercised when perindopril erbumine tablets are given to nursing mothers.
Pediatric Use:
Safety and effectiveness of perindopril erbumine tablets in pediatric patients have not been established.
Geriatric Use:
The mean blood pressure effect of perindopril was somewhat smaller in patients over 60 than in younger patients, although the difference was not significant. Plasma concentrations of both perindopril and perindoprilat were increased in elderly patients compared to concentrations in younger patients. No adverse effects were clearly increased in older patients with the exception of dizziness and possibly rash.
Perindopril should be used with caution when administered to elderly patients who are at an increased risk for falls due to age, their underlying disease and/or their concurrent use of medications(s) associated with falls. Falls and fall-related events may be exacerbated by the central nervous system effects of dizziness and syncope as well as the symptomatic hypotension, including orthostatic, associated with perindopril. Experience with perindopril erbumine tablets in elderly patients at daily doses exceeding 8 mg is limited.
What are the side effects of Perindopril Erbumine?
Hypertension
Perindopril erbumine tablets have been evaluated for safety in approximately 3,400 patients with hypertension in U.S. and foreign clinical trials. Perindopril erbumine tablets were in general well tolerated in the patient populations studied, the side effects were usually mild and transient. Although dizziness was reported more frequently in placebo patients (8.5%) than in perindopril patients (8.2%), the incidence appeared to increase with an increase in perindopril dose.
The data presented here are based on results from the 1,417 perindopril erbumine tablets -treated patients who participated in the U.S. clinical trials. Over 220 of these patients were treated with perindopril erbumine tablets for at least one year.
In placebo-controlled U.S. clinical trials, the incidence of premature discontinuation of therapy due to adverse events was 6.5% in patients treated with perindopril erbumine tablets and 6.7% in patients treated with placebo. The most common causes were cough, headache, asthenia and dizziness.
Among 1,012 patients in placebo-controlled U.S. trials, the overall frequency of reported adverse events was similar in patients treated with perindopril erbumine tablets and in those treated with placebo (approximately 75% in each group). Adverse events that occurred in 1% or greater of the patients and that were more common for perindopril than placebo by at least 1% (regardless of whether they were felt to be related to study drug) are shown in the first two columns below. Of these adverse events, those considered possibly or probably related to study drug are shown in the last two columns.
Of these, cough was the reason for withdrawal in 1.3% of perindopril and 0.4% of placebo patients. While dizziness was not reported more frequently in the perindopril group (8.2%) than in the placebo group (8.5%), it was clearly increased with dose, suggesting a causal relationship with perindopril. Other commonly reported complaints (1% or greater), regardless of causality, include: headache (23.8%), upper respiratory infection (8.6%), asthenia (7.9%), rhinitis (4.8%), low extremity pain (4.7%), diarrhea (4.3%), edema (3.9%), pharyngitis (3.3%), urinary tract infection (2.8%), abdominal pain (2.7%), sleep disorder (2.5%), chest pain (2.4%), injury, paresthesia, nausea, rash (each 2.3%), seasonal allergy, depression (each 2.0%), abnormal ECG (1.8%), ALT increase (1.7%), tinnitus, vomiting (each 1.5%), neck pain, male sexual dysfunction (each 1.4%), triglyceride increase, somnolence (each 1.3%), joint pain, nervousness, myalgia, menstrual disorder (each 1.1%), flatulence and arthritis (each 1.0%), but none of those was more frequent by at least 1% on perindopril than on placebo. Depending on the specific adverse event, approximately 30 to 70% of the common complaints were considered possibly or probably related to treatment.
Stable Coronary Artery Disease
Perindopril has been evaluated for safety in EUROPA, a double-blind, placebo-controlled study in 12,218 patients with stable coronary artery disease. The overall rate of discontinuation was about 22% on drug and placebo. The most common medical reasons for discontinuation that were more frequent on perindopril than placebo were cough, drug intolerance and hypotension.
Below is a list (by body system) of adverse experiences reported in 0.3 to 1% of patients in U.S. placebo-controlled studies in hypertensive patients without regard to attribution to therapy. Less frequent but medically important adverse events are also included; the incidence of these events is given in parentheses.
Body as a Whole:
Gastrointestinal:
Respiratory:
Urogenital:
Cardiovascular:
Endocrine:
Hematology:
Musculoskeletal:
CNS:
Psychiatric:
Dermatology:
Special Senses:
Laboratory:
When perindopril erbumine tablets was given concomitantly with thiazide diuretics, adverse events were generally reported at the same rate as those for perindopril erbumine tablets alone, except for a higher incidence of abnormal laboratory findings known to be related to treatment with thiazide diuretics alone (, increases in serum uric acid, triglycerides and cholesterol and decreases in serum potassium).
Potential Adverse Effects Reported with ACE Inhibitors:
Fetal/Neonatal Morbidity and Mortality:
Clinical Laboratory Test Findings
Hypertension
Hematology, clinical chemistry and urinalysis parameters have been evaluated in U.S. placebo-controlled trials. In general, there were no clinically significant trends in laboratory test findings.
Liver Function Tests:
| All Adverse Events | Related Adverse Events | |||
| Perindopril | Placebo | Perindopril | Placebo | |
| Cough | 12.0 | 4.5 | 6.0 | 1.8 |
| Back Pain | 5.8 | 3.1 | 0.0 | 0.0 |
| Sinusitis | 5.2 | 3.6 | 0.6 | 0.0 |
| Viral Infection | 3.4 | 1.6 | 0.3 | 0.0 |
| Upper Extremity Pain | 2.8 | 1.4 | 0.2 | 0.0 |
| Hypertonia | 2.7 | 1.4 | 0.2 | 0.0 |
| Dyspepsia | 1.9 | 0.9 | 0.3 | 0.0 |
| Fever | 1.5 | 0.5 | 0.3 | 0.0 |
| Proteinuria | 1.5 | 0.5 | 1.0 | 0.5 |
| Ear Infection | 1.3 | 0.0 | 0.0 | 0.0 |
| Palpitation | 1.1 | 0.0 | 0.9 | 0.0 |
What should I look out for while using Perindopril Erbumine?
Perindopril erbumine tablets are contraindicated in patients known to be hypersensitive to this product or to any other ACE inhibitor. Perindopril erbumine tablets are also contraindicated in patients with a history of angioedema related to previous treatment with an ACE inhibitor.
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 perindopril erbumine tablets) may be subject to a variety of adverse reactions, some of them serious.
Head and Neck Angioedema:
Angioedema involving the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with ACE inhibitors, including perindopril erbumine tablets (0.1% of patients treated with perindopril erbumine tablets in U.S. clinical trials). In such cases, perindopril erbumine tablets should be promptly discontinued and the patient carefully observed until the swelling disappears. 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 involvement of the tongue, glottis or larynx may be fatal due to airway obstruction. Appropriate therapy, such as subcutaneous epinephrine solution 1:1000 (0.3 to 0.5 mL), should be promptly administered. Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor.
Intestinal Angioedema:
Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.
Anaphylactoid Reactions During Desensitization:
Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge.
Anaphylactoid Reactions During Membrane Exposure:
Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.
Hypotension:
Like other ACE inhibitors, perindopril erbumine tablets can cause symptomatic hypotension. Perindopril erbumine tablets have been associated with hypotension in 0.3% of uncomplicated hypertensive patients in U.S. placebo-controlled trials. Symptoms related to orthostatic hypotension were reported in another 0.8% of patients.
Symptomatic hypotension associated with the use of ACE inhibitors is more likely to occur in patients who have been volume and/or salt-depleted, as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea or vomiting. Volume and/or salt depletion should be corrected before initiating therapy with perindopril erbumine tablets. (See .)
In patients with congestive heart failure, with or without associated renal insufficiency, ACE inhibitors may cause excessive hypotension, and may be associated with oliguria or azotemia, and rarely with acute renal failure and death. In patients with ischemic heart disease or cerebrovascular disease such an excessive fall in blood pressure could result in a myocardial infarction or a cerebrovascular accident.
In patients at risk of excessive hypotension, perindopril erbumine tablets therapy should be started under very close medical supervision. Patients should be followed closely for the first two weeks of treatment and whenever the dose of perindopril erbumine tablets and/or diuretic is increased.
If excessive hypotension occurs, the patient should be placed immediately in a supine position and, if necessary, treated with an intravenous infusion of physiological saline. Perindopril erbumine tablets treatment can usually be continued following restoration of volume and blood pressure.
Neutropenia/Agranulocytosis:
Another ACE 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 patients with a collagen vascular disease such as systemic lupus erythematosus or scleroderma. Available data from clinical trials of perindopril erbumine tablets are insufficient to show whether perindopril erbumine tablets causes agranulocytosis at similar rates.
What might happen if I take too much Perindopril Erbumine?
In animals, doses of perindopril up to 2,500 mg/kg in mice, 3,000 mg/kg in rats and 1,600 mg/kg in dogs were non-lethal. Past experiences were scant but suggested that overdosage with other ACE inhibitors was also fairly well tolerated by humans. The most likely manifestation is hypotension, and treatment should be symptomatic and supportive. Therapy with the ACE inhibitor should be discontinued, and the patient should be observed. Dehydration, electrolyte imbalance and hypotension should be treated by established procedures.
However, of the reported cases of perindopril overdosage, one (dosage unknown) required assisted ventilation and the other developed hypothermia, circulatory arrest and died following ingestion of up to 180 mg of perindopril. The intervention for perindopril overdose may require vigorous support (see below).
Laboratory determinations of serum levels of perindopril and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of perindopril overdose.
No data are available to suggest physiological maneuvers (, maneuvers to change the pH of the urine) that might accelerate elimination of perindopril and its metabolites. Perindopril can be removed by hemodialysis, with clearance of 52 mL/min for perindopril and 67 mL/min for perindoprilat.
Angiotensin II could presumably serve as a specific antagonist-antidote in the settling of perindopril overdose, but angiotensin II is essentially unavailable outside of scattered research facilities. Because the hypotensive effect of perindopril is achieved through vasodilation and effective hypovolemia, it is reasonable to treat perindopril overdose by infusion of normal saline solution.
How should I store and handle Perindopril Erbumine?
Store bottles of 1000 SINGULAIR 5-mg chewable tablets and 8000 SINGULAIR 10-mg film-coated tablets at 25°C (77°F), excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Protect from moisture and light. Store in original container. When product container is subdivided, repackage into a well-closed, light resistant container. Perindopril Erbumine Tablets are supplied as below: Storage Conditions: Keep out of the reach of children. Manufactured for: Baltimore, Maryland 21202 United States Manufactured by: Goa - 403 722 INDIA Revision Date: January 2010 Item Code: 21207Perindopril Erbumine Tablets are supplied as below: Storage Conditions: Keep out of the reach of children. Manufactured for: Baltimore, Maryland 21202 United States Manufactured by: Goa - 403 722 INDIA Revision Date: January 2010 Item Code: 21207Perindopril Erbumine Tablets are supplied as below: Storage Conditions: Keep out of the reach of children. Manufactured for: Baltimore, Maryland 21202 United States Manufactured by: Goa - 403 722 INDIA Revision Date: January 2010 Item Code: 21207Perindopril Erbumine Tablets are supplied as below: Storage Conditions: Keep out of the reach of children. Manufactured for: Baltimore, Maryland 21202 United States Manufactured by: Goa - 403 722 INDIA Revision Date: January 2010 Item Code: 21207Perindopril Erbumine Tablets are supplied as below: Storage Conditions: Keep out of the reach of children. Manufactured for: Baltimore, Maryland 21202 United States Manufactured by: Goa - 403 722 INDIA Revision Date: January 2010 Item Code: 21207Perindopril Erbumine Tablets are supplied as below: Storage Conditions: Keep out of the reach of children. Manufactured for: Baltimore, Maryland 21202 United States Manufactured by: Goa - 403 722 INDIA Revision Date: January 2010 Item Code: 21207
Clinical Information
Chemical Structure
No Image foundClinical Pharmacology
Perindopril erbumine tablets are a pro-drug for perindoprilat, which inhibits ACE in human subjects and animals. The mechanism through which perindoprilat lowers blood pressure is believed to be primarily inhibition of ACE activity. ACE is a peptidyl dipeptidase that catalyzes conversion of the inactive decapeptide, angiotensin I, to the vasoconstrictor, angiotensin II. Angiotensin II is a potent peripheral vasoconstrictor, which stimulates aldosterone secretion by the adrenal cortex, and provides negative feedback on renin secretion. Inhibition of ACE results in decreased plasma angiotensin II, leading to decreased vasoconstriction, increased plasma renin activity and decreased aldosterone secretion. The latter results in diuresis and natriuresis and may be associated with a small increase of serum potassium.
ACE is identical to kininase II, an enzyme that degrades bradykinin. Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of perindopril erbumine tablets remains to be elucidated.
While the principal mechanism of perindopril in blood pressure reduction is believed to be through the renin-angiotensin-aldosterone system, ACE inhibitors have some effect even in apparent low-renin hypertension. Perindopril has been studied in relatively few black patients, usually a low-renin population, and the average response of diastolic blood pressure to perindopril was about half the response seen in nonblacks, a finding consistent with previous experience of other ACE inhibitors.
After administration of perindopril, ACE is inhibited in a dose and blood concentration-related fashion, with the maximal inhibition of 80 to 90% attained by 8 mg persisting for 10 to 12 hours. Twenty-four hour ACE inhibition is about 60% after these doses. The degree of ACE inhibition achieved by a given dose appears to diminish over time (the ID increases). The pressor response to an angiotensin I infusion is reduced by perindopril, but this effect is not as persistent as the effect on ACE; there is about 35% inhibition at 24 hours after a 12 mg dose.
Non-Clinical Toxicology
Perindopril erbumine tablets are contraindicated in patients known to be hypersensitive to this product or to any other ACE inhibitor. Perindopril erbumine tablets are also contraindicated in patients with a history of angioedema related to previous treatment with an ACE inhibitor.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 perindopril erbumine tablets) may be subject to a variety of adverse reactions, some of them serious.
Head and Neck Angioedema:
Angioedema involving the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with ACE inhibitors, including perindopril erbumine tablets (0.1% of patients treated with perindopril erbumine tablets in U.S. clinical trials). In such cases, perindopril erbumine tablets should be promptly discontinued and the patient carefully observed until the swelling disappears. 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 involvement of the tongue, glottis or larynx may be fatal due to airway obstruction. Appropriate therapy, such as subcutaneous epinephrine solution 1:1000 (0.3 to 0.5 mL), should be promptly administered. Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor.
Intestinal Angioedema:
Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.
Anaphylactoid Reactions During Desensitization:
Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge.
Anaphylactoid Reactions During Membrane Exposure:
Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.
Hypotension:
Like other ACE inhibitors, perindopril erbumine tablets can cause symptomatic hypotension. Perindopril erbumine tablets have been associated with hypotension in 0.3% of uncomplicated hypertensive patients in U.S. placebo-controlled trials. Symptoms related to orthostatic hypotension were reported in another 0.8% of patients.
Symptomatic hypotension associated with the use of ACE inhibitors is more likely to occur in patients who have been volume and/or salt-depleted, as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea or vomiting. Volume and/or salt depletion should be corrected before initiating therapy with perindopril erbumine tablets. (See .)
In patients with congestive heart failure, with or without associated renal insufficiency, ACE inhibitors may cause excessive hypotension, and may be associated with oliguria or azotemia, and rarely with acute renal failure and death. In patients with ischemic heart disease or cerebrovascular disease such an excessive fall in blood pressure could result in a myocardial infarction or a cerebrovascular accident.
In patients at risk of excessive hypotension, perindopril erbumine tablets therapy should be started under very close medical supervision. Patients should be followed closely for the first two weeks of treatment and whenever the dose of perindopril erbumine tablets and/or diuretic is increased.
If excessive hypotension occurs, the patient should be placed immediately in a supine position and, if necessary, treated with an intravenous infusion of physiological saline. Perindopril erbumine tablets treatment can usually be continued following restoration of volume and blood pressure.
Neutropenia/Agranulocytosis:
Another ACE 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 patients with a collagen vascular disease such as systemic lupus erythematosus or scleroderma. Available data from clinical trials of perindopril erbumine tablets are insufficient to show whether perindopril erbumine tablets causes agranulocytosis at similar rates.
The rate and extent of perindopril absorption and elimination are not affected by concomitant diuretics. The bioavailability of perindoprilat was reduced by diuretics, however, and this was associated with a decrease in plasma ACE inhibition.
Impaired Renal Function:
Hypertensive Patients with Congestive Heart Failure:
Hypertensive Patients with Renal Artery Stenosis:
Some hypertensive patients without apparent pre-existing renal vascular disease have developed increases in blood urea nitrogen and serum creatinine, usually minor and transient. These increases are more likely to occur in patients treated concomitantly with a diuretic and in patients with pre-existing renal impairment. Reduction of dosages of perindopril erbumine tablets, the diuretic or both may be required. In some cases, discontinuation of either or both drugs may be necessary.
Evaluation of hypertensive patients should always include an assessment of renal function. (See .)
Cough:
Surgery/Anesthesia:
Information for Patients:
Angioedema:
Symptomatic Hypotension:
All patients should be cautioned that inadequate fluid intake or excessive perspiration, diarrhea or vomiting can lead to an excessive fall in blood pressure in association with ACE inhibitor therapy.
Hyperkalemia:
e.g.
Pregnancy:
Hypertension
Perindopril erbumine tablets have been evaluated for safety in approximately 3,400 patients with hypertension in U.S. and foreign clinical trials. Perindopril erbumine tablets were in general well tolerated in the patient populations studied, the side effects were usually mild and transient. Although dizziness was reported more frequently in placebo patients (8.5%) than in perindopril patients (8.2%), the incidence appeared to increase with an increase in perindopril dose.
The data presented here are based on results from the 1,417 perindopril erbumine tablets -treated patients who participated in the U.S. clinical trials. Over 220 of these patients were treated with perindopril erbumine tablets for at least one year.
In placebo-controlled U.S. clinical trials, the incidence of premature discontinuation of therapy due to adverse events was 6.5% in patients treated with perindopril erbumine tablets and 6.7% in patients treated with placebo. The most common causes were cough, headache, asthenia and dizziness.
Among 1,012 patients in placebo-controlled U.S. trials, the overall frequency of reported adverse events was similar in patients treated with perindopril erbumine tablets and in those treated with placebo (approximately 75% in each group). Adverse events that occurred in 1% or greater of the patients and that were more common for perindopril than placebo by at least 1% (regardless of whether they were felt to be related to study drug) are shown in the first two columns below. Of these adverse events, those considered possibly or probably related to study drug are shown in the last two columns.
Of these, cough was the reason for withdrawal in 1.3% of perindopril and 0.4% of placebo patients. While dizziness was not reported more frequently in the perindopril group (8.2%) than in the placebo group (8.5%), it was clearly increased with dose, suggesting a causal relationship with perindopril. Other commonly reported complaints (1% or greater), regardless of causality, include: headache (23.8%), upper respiratory infection (8.6%), asthenia (7.9%), rhinitis (4.8%), low extremity pain (4.7%), diarrhea (4.3%), edema (3.9%), pharyngitis (3.3%), urinary tract infection (2.8%), abdominal pain (2.7%), sleep disorder (2.5%), chest pain (2.4%), injury, paresthesia, nausea, rash (each 2.3%), seasonal allergy, depression (each 2.0%), abnormal ECG (1.8%), ALT increase (1.7%), tinnitus, vomiting (each 1.5%), neck pain, male sexual dysfunction (each 1.4%), triglyceride increase, somnolence (each 1.3%), joint pain, nervousness, myalgia, menstrual disorder (each 1.1%), flatulence and arthritis (each 1.0%), but none of those was more frequent by at least 1% on perindopril than on placebo. Depending on the specific adverse event, approximately 30 to 70% of the common complaints were considered possibly or probably related to treatment.
Stable Coronary Artery Disease
Perindopril has been evaluated for safety in EUROPA, a double-blind, placebo-controlled study in 12,218 patients with stable coronary artery disease. The overall rate of discontinuation was about 22% on drug and placebo. The most common medical reasons for discontinuation that were more frequent on perindopril than placebo were cough, drug intolerance and hypotension.
Below is a list (by body system) of adverse experiences reported in 0.3 to 1% of patients in U.S. placebo-controlled studies in hypertensive patients without regard to attribution to therapy. Less frequent but medically important adverse events are also included; the incidence of these events is given in parentheses.
Body as a Whole:
Gastrointestinal:
Respiratory:
Urogenital:
Cardiovascular:
Endocrine:
Hematology:
Musculoskeletal:
CNS:
Psychiatric:
Dermatology:
Special Senses:
Laboratory:
When perindopril erbumine tablets was given concomitantly with thiazide diuretics, adverse events were generally reported at the same rate as those for perindopril erbumine tablets alone, except for a higher incidence of abnormal laboratory findings known to be related to treatment with thiazide diuretics alone (, increases in serum uric acid, triglycerides and cholesterol and decreases in serum potassium).
Potential Adverse Effects Reported with ACE Inhibitors:
Fetal/Neonatal Morbidity and Mortality:
Clinical Laboratory Test Findings
Hypertension
Hematology, clinical chemistry and urinalysis parameters have been evaluated in U.S. placebo-controlled trials. In general, there were no clinically significant trends in laboratory test findings.
Liver Function Tests:
Reference
This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"
While we update our database periodically, we cannot guarantee it is always updated to the latest version.
Review
Read user comments about the side effects, benefits, and effectiveness of losartan oral.
Overall User Ratings
514Total User Reviews
User Reviews
Learn about
User Reviews
Professional
Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72Tips
Tips
Interactions
Interactions
A total of 440 drugs (1549 brand and generic names) are known to interact with Imbruvica (ibrutinib). 228 major drug interactions (854 brand and generic names) 210 moderate drug interactions (691 brand and generic names) 2 minor drug interactions (4 brand and generic names) Show all medications in the database that may interact with Imbruvica (ibrutinib).