What happens if I overdose Périndopril?
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include fainting; severe dizziness or light-headedness; weakness.
Proper storage of Périndopril:
Store Périndopril at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, light, and moisture. Do not store in the bathroom. Keep Périndopril out of the reach of children and away from pets.
Overdose of Périndopril in details
In animals, doses of Périndopril 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.
Among the reported cases of Périndopril overdosage, patients who were known to have ingested a dose of 80 mg to 120 mg required assisted ventilation and circulatory support. One additional patient developed hypothermia, circulatory arrest and died following ingestion of up to 180 mg of Périndopril. The intervention for Périndopril overdose may require vigorous support.
Laboratory determinations of serum levels of Périndopril and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of Périndopril overdose.
No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of Périndopril and its metabolites. Périndopril can be removed by hemodialysis, with clearance of 52 mL/min for Périndopril and 67 mL/min for Perindoprilat.
Angiotensin II could presumably serve as a specific antagonist-antidote in the settling of Périndopril overdose, but angiotensin II is essentially unavailable outside of scattered research facilities. Because the hypotensive effect of Périndopril is achieved through vasodilation and effective hypovolemia, it is reasonable to treat Périndopril overdose by infusion of normal saline solution.
What should I avoid while taking Périndopril?
Drinking alcohol can further lower your blood pressure and may increase certain side effects of Périndopril.
Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.
Do not use salt substitutes or potassium supplements while taking Périndopril, unless your doctor has told you to.
Périndopril warnings
Anaphylactoid and Possibly Related Reactions
Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including Périndopril) may be subject to a variety of adverse events, some of them serious. Black patients receiving ACE inhibitors have a higher incidence of angioedema compared to nonblacks.
Head and Neck Angioedema: Angioedema of the face, extremities, lips, tongue, glottis, or larynx has been reported in patients treated with ACE inhibitors, including Périndopril (0.1% of patients treated with Périndopril in U.S. clinical trials). Angioedema associated with involvement of the tongue, glottis or larynx may be fatal. In such cases, discontinue Périndopril treatment immediately and observe until the swelling disappears. When involvement of the tongue, glottis, or larynx appears likely to cause airway obstruction, administer appropriate therapy, such as subcutaneous epinephrine solution 1:1000 (0.3 to 0.5 mL), promptly.
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.
Hypotension
Périndopril can cause symptomatic hypotension. Périndopril has 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 is most likely to occur in patients who have been volume or salt-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea or vomiting.
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, an excessive fall in blood pressure could result in a myocardial infarction or a cerebrovascular accident.
In patients at risk of excessive hypotension, Périndopril 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 Périndopril 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. Périndopril treatment can usually be continued following restoration of volume and blood pressure.
Neutropenia/Agranulocytosis
ACE inhibitors have been associated with agranulocytosis and bone marrow depression, most frequently in patients with renal impairment, especially patients with a collagen vascular disease such as systemic lupus erythematosus or scleroderma.
Fetal Toxicity
Pregnancy Category D
Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected discontinue Périndopril as soon as possible.
Impaired Renal Function
As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. Renal function should be monitored periodically in patients receiving Périndopril,.
In patients with severe congestive heart failure, where renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with ACE inhibitors, including Périndopril, may be associated with oliguria, progressive azotemia, and, rarely, acute renal failure and death.
In hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine may occur; usually reversible upon discontinuation of the ACE inhibitor. In such patients, renal function should be monitored during the first few weeks of therapy.
Some Périndopril-treated patients have developed minor and transient increases in blood urea nitrogen and serum creatinine especially in those concomitantly treated with a diuretic.
Hyperkalemia
Elevations of serum potassium have been observed in some patients treated with ACE inhibitors, including Périndopril. Most cases were isolated single values that did not appear clinically relevant and were rarely a cause for withdrawal. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus and the concomitant use of agents such as potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes.
Serum potassium should be monitored periodically in patients receiving Périndopril.
Cough
Presumably because of the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, generally resolving after discontinuation of therapy. Consider ACE inhibitor-induced cough in the differential diagnosis of cough.
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.
Surgery/Anesthesia
In patients undergoing surgery or during anesthesia with agents that produce hypotension, Périndopril may block angiotensin II formation that would otherwise occur secondary to compensatory renin release. Hypotension attributable to this mechanism can be corrected by volume expansion.
What should I discuss with my healthcare provider before taking Périndopril?
Do not use this medication if you are allergic to Périndopril or to any other ACE inhibitor, such as benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, quinapril, ramipril, or trandolapril.
If you have diabetes, do not use Périndopril together with any medication that contains aliskiren (Amturnide, Tekturna, Tekamlo, Valturna).
You may also need to avoid taking Périndopril with aliskiren if you have kidney disease.
You should not use Périndopril if you have hereditary angioedema.
To make sure you can safely take Périndopril, tell your doctor if you have any of these other conditions:
-
kidney disease (or if you are on dialysis);
-
liver disease;
-
heart disease or congestive heart failure;
-
diabetes; or
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a connective tissue disease such as Marfan syndrome, Sjogren's syndrome, lupus, scleroderma, or rheumatoid arthritis.
FDA pregnancy category D. Do not use Périndopril if you are pregnant. Stop using this medication and tell your doctor right away if you become pregnant. Périndopril can cause injury or death to the unborn baby if you take the medicine during your second or third trimester. Use effective birth control while taking Périndopril.
It is not known whether Périndopril passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.
Périndopril precautions
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 Périndopril) may be subject to a variety of adverse events, some of them serious. Black patients receiving ACE inhibitors have a higher incidence of angioedema compared to nonblacks.
Head and Neck Angioedema: Angioedema of the face, extremities, lips, tongue, glottis, or larynx has been reported in patients treated with ACE inhibitors, including Périndopril (0.1% of patients treated with Périndopril in U.S. clinical trials). Angioedema associated with involvement of the tongue, glottis or larynx may be fatal. In such cases, discontinue Périndopril treatment immediately and observe until the swelling disappears. When involvement of the tongue, glottis, or larynx appears likely to cause airway obstruction, administer appropriate therapy, such as subcutaneous epinephrine solution 1:1000 (0.3 to 0.5 mL), promptly.
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.
Hypotension
Périndopril can cause symptomatic hypotension. Périndopril has 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 is most likely to occur in patients who have been volume or salt-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea or vomiting.
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, an excessive fall in blood pressure could result in a myocardial infarction or a cerebrovascular accident.
In patients at risk of excessive hypotension, Périndopril 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 Périndopril 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. Périndopril treatment can usually be continued following restoration of volume and blood pressure.
Neutropenia/Agranulocytosis
ACE inhibitors have been associated with agranulocytosis and bone marrow depression, most frequently in patients with renal impairment, especially patients with a collagen vascular disease such as systemic lupus erythematosus or scleroderma.
Fetal Toxicity
Pregnancy Category D
Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected discontinue Périndopril as soon as possible.
Impaired Renal Function
As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. Renal function should be monitored periodically in patients receiving Périndopril,.
In patients with severe congestive heart failure, where renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with ACE inhibitors, including Périndopril, may be associated with oliguria, progressive azotemia, and, rarely, acute renal failure and death.
In hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine may occur; usually reversible upon discontinuation of the ACE inhibitor. In such patients, renal function should be monitored during the first few weeks of therapy.
Some Périndopril-treated patients have developed minor and transient increases in blood urea nitrogen and serum creatinine especially in those concomitantly treated with a diuretic.
Hyperkalemia
Elevations of serum potassium have been observed in some patients treated with ACE inhibitors, including Périndopril. Most cases were isolated single values that did not appear clinically relevant and were rarely a cause for withdrawal. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus and the concomitant use of agents such as potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes.
Serum potassium should be monitored periodically in patients receiving Périndopril.
Cough
Presumably because of the inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, generally resolving after discontinuation of therapy. Consider ACE inhibitor-induced cough in the differential diagnosis of cough.
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.
Surgery/Anesthesia
In patients undergoing surgery or during anesthesia with agents that produce hypotension, Périndopril may block angiotensin II formation that would otherwise occur secondary to compensatory renin release. Hypotension attributable to this mechanism can be corrected by volume expansion.
What happens if I miss a dose of Périndopril?
Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
References
- DrugBank. "PERINDOPRIL". http://www.drugbank.ca/drugs/DB00790 (accessed September 17, 2018).
- MeSH. "Antihypertensive Agents". https://www.ncbi.nlm.nih.gov/mesh/68... (accessed September 17, 2018).
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Information checked by Dr. Sachin Kumar, MD Pharmacology
