Ramipril (ramipril)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Ramipril is a nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor.
Ramipril is an angiotensin-converting enzyme (ACE) inhibitor. Ramipril is a prodrug with little pharmacologic activity until metabolism in the liver to ramiprilat, which has 6 times the ACE inhibitory activity of ramipril. Ramiprilat prevents the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor) through inhibition of ACE.
Inhibition of ACE results in decreased plasma angiotensin II concentrations and, consequently, blood pressure may be reduced in part through decreased vasoconstriction. Because of decreased plasma angiotensin II concentrations, plasma renin activity (PRA) increases. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex.
With decreased plasma angiotensin II concentrations, small increases in serum potassium can be observed.
While the mechanism by which ramipril lowers blood pressure is thought to be from suppression of the renin-angiotensin-aldosterone system, ramipril may also lower blood pressure in patients with low-renin hypertension. Although ramipril has lowered blood pressure in all races studied, the drug was less effective in Black hypertensive patients, a population associated with low renin hypertension. Because ACE is identical to 'kininase,' ramipril may also interfere with degradation of the vasodepressor peptide bradykinin.
Whether increased concentrations of bradykinin play a role in the therapeutic efficacy of ramipril remains to be elucidated.
Following oral administration of ramipril, peak plasma concentrations occur in about 1 hour. The 24-hour AUC is dose-proportional over the oral dose range of 2.5-20 mg. Approximately 50-60% of an oral ramipril dose is absorbed from the GI tract, and foods affects the rate but not the extent of absorption.
In a study where ramipril capsules were dissolved in water, apple juice, or suspended in apple sauce, serum ramiprilat levels were similar to those observed in patients who did not receive dissolved capsules or food. Peak plasma concentrations of ramiprilat are attained 2-4 hours after oral intake. Individual doses of ramipril inhibit 60-80% of ACE activity 4 hours after dosing, with 40-60% inhibition noted after 24 hours.
Multiple oral doses of at least 2 mg of ramipril inhibit more than 90% of ACE activity 4 hours after dosing, with over 80% of ACE activity still inhibited after 24 hours. With once daily dosing, steady state concentrations are attained by the fourth dose.
Ramipril is 73% bound to plasma proteins; ramiprilat is 56% protein bound. Plasma concentrations of ramiprilat decline in a triphasic manner. Following an initial rapid decline where the drug distributes into a large peripheral compartment, the apparent elimination phase, or the clearance of free ramiprilat, has a half-life of 9-18 hours.
The terminal elimination phase, which corresponds to the binding and/or dissociation of ramipril from the ACE complex, has a prolonged half-life of >50 hours. Following multiple daily doses of 5-10 mg, the elimination half-life of ramiprilat concentrations within the therapeutic range is approximately 13-17 hours.
In people with a creatinine clearance of less than 40 mL/minute/1.73 m2, peak levels of ramiprilat are about doubled, and trough levels may almost quintuple. In multiple-dose regimens, the total ramiprilat exposure based on AUC is 3-4 times that observed in normal renal function. In patients with hepatic impairment, the metabolism of ramipril to ramiprilat is slowed, and plasma ramipril levels increase approximately 3-fold.
Peak concentrations of ramiprilat, however, and the effect on plasma ACE activity are similar to that in normal hepatic function.
Following oral administration of ramipril, 60% of the parent drug and its metabolites are excreted in the urine (<2% as unchanged ramipril), and 40% is excreted in the feces. Urinary excretion of ramipril, ramiprilat, and their metabolites is reduced in renal impairment. Patients with a creatinine clearance of less than 40 mL/minute/1.73 m2 had higher peak and trough ramiprilat concentrations and slightly longer times to peak concentrations.
USES: This medication is used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. This medication is also used to improve survival after a heart attack.
It may also be used in high risk patients (such as patients with heart disease/diabetes) to help prevent heart attacks and strokes. This medication may also be used to treat heart failure in patients who have had a recent heart attack. Ramipril belongs to a class of drugs known as ACE inhibitors.
It works by relaxing blood vessels so blood can flow more easily.
Generic name: ramipril
Pronunciation: (RAM-ih-prill)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Ramipril
Indications
The following indications are listed for Ramipril:
- Chronic Heart Failure Following Myocardial Infarction
- Hypertension
- Left Ventricular Dysfunction Following Myocardial Infarction
- Myocardial Infarction Prevention
- Prevention Of Cerebrovascular Accident
Also known as: Acute Mi Prophylaxis, Acute Myocardial Infarction Prophylaxis, Ami Prophylaxis, Cardiac Infarct Prophylaxis, Cardiac Infarction Prophylaxis, Chf Following Mi, Congestive Heart Failure Resulting From Myocardial Infarction, Cva Prophylaxis, Elevated Blood Pressure, Essential Hypertension, Hyperpiesia, Hyperpiesis, Hypertensive Disorder, Left Ventricular Dysfunction Following Acute Mi, Left Ventricular Dysfunction Following Acute Myocardial Infarction, Left Ventricular Dysfunction Following Ami, Left Ventricular Dysfunction Following Cardiac Infarct, Left Ventricular Dysfunction Following Cardiac Infarction, Left Ventricular Dysfunction Following Myocardial Infarct, Lv Dysfunction Following Mi, Mi Prophylaxis, Myocardial Infarct Prophylaxis, Myocardial Infarction Prophylaxis, Stroke Prophylaxis, Systemic Arterial Hypertension.
Dosing
No dosing information is available for this tab.
Ramipril is administered orally.
Ramipril is commercially available as capsules and an oral solution.
Administration with food may decrease the rate but not the extent of GI absorption of the drug.
Ramipril capsules usually are swallowed whole. If needed, the capsules may be opened and the contents sprinkled in a small amount (about 120 mL) of applesauce or mixed in 120 mL of water or apple juice. To ensure that no drug is lost, the entire mixture should be consumed. These mixtures are stable for 24 hours at room temperature and 48 hours when refrigerated.
Store ramipril capsules at 20-25oC in a tight, light-resistant container with child-resistant closure.
Store ramipril oral solution in the refrigerator at 2-8oC in the original packaging. Once the bottle is opened, the solution may be stored at 20-25oC and should be used within 60 days.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*History of angioedema related to previous angiotensin-converting enzyme (ACE) inhibitor treatment.
*Known hypersensitivity to ramipril, other ACE inhibitors, or any ingredient in the formulation.
*Concomitant use (within 36 hours) of a neprilysin inhibitor (e.g., sacubitril).
*Concomitant use of aliskiren in patients with diabetes mellitus.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in 1% or more of patients receiving ramipril include asthenia/fatigue, hypotension, postural hypotension, increased cough, dizziness, headache, angina pectoris, nausea, syncope, vomiting, vertigo, abnormal kidney function, and diarrhea.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
The manufacturers state that safety and efficacy of ramipril in pediatric patients younger than 18 years of age have not been established.
Infants exposed in utero to ACE inhibitors should be observed closely for hypotension, oliguria, and hyperkalemia. If oliguria occurs, supportive measures (e.g., administration of fluids and pressor agents) to correct hypotension and renal perfusion should be considered. Exchange transfusion or dialysis may be required to reverse hypotension and/or substitute for impaired renal function. Ramipril, which crosses the placenta, has been removed from neonatal circulation by peritoneal dialysis with some clinical benefit. The manufacturer states that the drug theoretically may be removed by exchange transfusion; however, this latter procedure has not been used to date.
Drugs that act on the renin-angiotensin system (e.g., ACE inhibitors, angiotensin II receptor antagonists) reduce fetal renal function and increase fetal and neonatal morbidity and mortality when used during the second and third trimesters of pregnancy. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal effects include skull hypoplasia, anuria, hypotension, renal failure, and death. Most epidemiologic data evaluating antihypertensive use in the first trimester and the development of fetal abnormalities have not differentiated a risk between medications affecting the renin-angiotensin system and other antihypertensive agents.
Appropriate management of maternal hypertension during pregnancy is necessary to optimize outcomes for the mother and fetus. Discontinue ACE inhibitors (e.g., ramipril) as soon as possible when pregnancy is detected. In the rare situation that use of ramipril is deemed necessary, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intraamniotic environment. Fetal testing may be appropriate, based on the week of pregnancy; however, oligohydramnios may not appear until after the fetus has sustained irreversible injury. If oligohydramnios is observed, discontinue ramipril unless it is considered lifesaving for the mother. Closely observe infants with histories of in utero exposure to ramipril for hypotension, oliguria, and hyperkalemia.
Ramipril and its metabolites were undetectable in breast milk following a single 10-mg oral dose of the drug in nursing women; however, milk concentrations resulting from multiple doses of the drug have not been determined.
Because of the potential for serious adverse reactions from ramipril in nursing infants, the manufacturers state that women receiving the drug should not breast-feed.
The manufacturer makes no specific dosage recommendations in geriatric patients.
No substantial differences in safety and efficacy have been observed in geriatric patients relative to younger adults, but increased sensitivity cannot be ruled out. Increased ramiprilat plasma concentrations and AUC have been reported in some geriatric patients.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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