Altace

Name: Altace

Other uses for this medicine

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

In case of emergency/overdose

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include the following:

  • lightheadedness
  • fainting

What other information should I know?

Keep all appointments with your doctor and the laboratory. Your blood pressure should be checked regularly to determine your response to ramipril. Your doctor may order certain lab tests to check your body's response to ramipril.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

What else should I know about ramipril?

What preparations of ramipril are available?

Capsules or tablets: 1.25, 2.5, 5 and 10 mg

How should I keep ramipril stored?

Tablets and capsules should be stored at room temperature between 15 C to 30 C (59 F to 86 F).

Missed dose

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

Adverse Effects

>10%

Cough (7-8%)

Hypotension (2-11%)

1-10%

Headache (1-5%)

Angina pectoris (3%)

Dizziness (2-4%)

Nausea (2%)

Vomiting (2%)

Postural hypotension (2%)

Syncope (2%)

Vertigo (2%)

Abnormal kidney function (1%)

Diarrhea (1%)

<1%

Angioedema (0.3%)

Pregnancy & Lactation

Pregnancy category: D

Discontinue as soon as pregnancy detected; during the second and third trimesters of pregnancy, therapy can result in fetal injury (eg, hypotension, neonatal skull hypoplasia, anuria, reversible and irreversible renal failure) and death

Lactation: Possibly excreted in breast milk; nursing not recommended

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Side Effects of Altace

Serious side effects have been reported with Altace. See “Altace Precautions” section.

Common side effects of Altace include headache, fatigue, dizziness, and cough.

This is not a complete list of Altace side effects. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Altace and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Altace falls into category D. It has been shown that use of Altace in pregnant women caused some babies to be born with problems. More specifically, it has been shown that use of drugs like Altace during the second and third trimesters of pregnancy harms the unborn baby’s kidneys and even increases the risk of death to the unborn baby. However, in some serious situations, the benefit of using this medication may be greater than the risk of harm to the baby.

Altace FDA Warning

  • When pregnancy is detected, discontinue Altace as soon as possible.
  • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.

What should I discuss with my healthcare provider before taking ramipril?

You should not use this medication if you are allergic to ramipril or to any other ACE inhibitor, such as benazepril, captopril, fosinopril, enalapril, lisinopril, moexipril, perindopril, quinapril, or trandolapril.

If you have diabetes, do not use ramipril together with any medication that contains aliskiren (such as Amturnide, Tekturna, Tekamlo).

You may also need to avoid taking ramipril with aliskiren if you have kidney disease.

To make sure ramipril is safe for you, tell your doctor if you have:

  • kidney disease (or if you are on dialysis);

  • liver disease;

  • diabetes;

  • a connective tissue disease such as Marfan syndrome, Sjogren's syndrome, lupus, scleroderma, or rheumatoid arthritis; or

  • if you are also taking telmisartan (Micardis).

Do not use if you are pregnant. If you become pregnant, stop taking this medicine and tell your doctor right away. Ramipril can cause injury or death to the unborn baby if you take the medicine during your second or third trimester.

It is not known whether ramipril passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

How should I take ramipril?

Follow all directions on your prescription label. Your doctor may occasionally change your dose. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Ramipril can be taken with or without food.

Swallow the ramipril tablet whole.

You may open the ramipril capsule and sprinkle the medicine into a half-cup (4 ounces) of water, apple juice, or applesauce to make swallowing easier. Swallow without chewing. You may store the mixture for up to 24 hours at room temperature, or up to 48 hours in a refrigerator.

Call your doctor if you have ongoing vomiting or diarrhea, or if you are sweating more than usual. You can easily become dehydrated while taking ramipril. This can lead to very low blood pressure, electrolyte disorders, or kidney failure.

Your blood pressure will need to be checked often, and you may need frequent blood tests to check your potassium levels.

Drink plenty of water each day while you are taking this medication.

If you need surgery, tell the surgeon ahead of time that you are using ramipril. You may need to stop using the medicine for a short time.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Store at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.

Altace Dosage and Administration

General

BP Monitoring and Treatment Goals

  • Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.500 501

  • When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501

  • If adequate BP response not achieved with a single antihypertensive agent, add a second drug with demonstrated benefit; if goal BP still not achieved with optimal dosages of 2 antihypertensive agents, add a third drug.501 May maximize dosage of the first drug before adding a second drug, or add a second drug before maximizing dosage of the initial drug.501

  • Consider initiating antihypertensive therapy with a combination of drugs if patient's BP exceeds goal BP by >20/10 mm Hg.500 501 503 504

  • Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501 (See Hypertension under Uses.)

Administration

Oral Administration

Administer orally once or twice daily.1

Swallow capsules whole.1 Alternatively, open capsules and sprinkle contents on small amount (about 120 mL) of applesauce or mix in 120 mL of water or apple juice.1 Consume entire mixture to ensure that no drug is lost.1 (See Storage under Stability.)

Dosage

In patients currently receiving diuretic therapy, discontinue diuretic, reduce diuretic dosage, or increase salt intake prior to initiating ramipril.600 If such changes are not possible, initiate ramipril in adults at a reduced dosage of 1.25 mg once daily.600 (See Hypotension under Cautions and see the individual dosage sections in Dosage and Administration.)

Adults

Hypertension Oral

Initially, 2.5 mg once daily in patients not receiving diuretic therapy.600 In patients receiving a diuretic, initiate ramipril at 1.25 mg once daily.600 Adjust subsequent dosage based on BP response.600

Usual maintenance dosage: 2.5–20 mg daily, given in 1 dose or 2 divided doses.500 600

If effectiveness diminishes toward end of dosing interval in patients treated once daily, consider increasing dosage or administering drug in 2 divided doses.600

If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501

Mortality Reduction after Acute MI with Heart Failure Oral

Initially, 2.5 mg twice daily, beginning as early as 2 days after MI.1 12 If hypotension occurs, reduce dosage to 1.25 mg twice daily.1 After 1 week at initial dosage, adjust dosage as tolerated at 3-week intervals to target dosage of 5 mg twice daily.1

Following initial dose, monitor closely for ≥2 hours and until BP has stabilized for at least an additional hour.1 To minimize risk of hypotension, reduce diuretic dosage, if possible.1

Prevention of Major Cardiovascular Events Oral

Initially, 2.5 mg once daily for 1 week, followed by 5 mg once daily for 3 weeks; subsequently increase dosage as tolerated to maintenance dosage of 10 mg once daily.1 In patients with hypertension or those with recent MI, may administer total daily dosage in divided doses.1

Heart Failure† Oral

Initially, 1.25–2.5 mg once daily recommended by ACCF and AHA in patients with prior or current symptoms of chronic heart failure and reduced LVEF (ACCF/AHA stage C heart failure).524

Titrate dosage slowly upward as tolerated to dosages shown to reduce the risk of cardiovascular events in clinical trials; may use intermediate doses if such target dosages cannot be achieved or are poorly tolerated.524

ACCF and AHA recommend maximum ramipril dosage of 10 mg once daily for patients with ACCF/AHA stage C heart failure.524

Special Populations

Renal Impairment

Initial dosage of 1.25 mg once daily recommended in patients with renal artery stenosis.1

In patients with Clcr <40 mL/minute, 25% of the usual doses are expected to induce full therapeutic concentrations of ramiprilat.1

Hypertension Oral

Initially, 1.25 mg once daily in patients with Clcr <40 mL/minute.1 Titrate until BP is controlled or to maximum dosage of 5 mg daily.1

Mortality Reduction After Acute MI with Heart Failure Oral

Initially, 1.25 mg once daily in patients with Clcr <40 mL/minute.1 May increase dosage to 1.25 mg twice daily; subsequently titrate according to clinical response and tolerance up to maximum dosage of 2.5 mg twice daily.1

Volume-and/or Salt-Depleted Patients

Correct volume and/or salt depletion prior to initiation of therapy or initiate therapy at dosage of 1.25 mg once daily.1

What are some things I need to know or do while I take Altace?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how Altace affects you.
  • To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
  • Have your blood pressure checked often. Talk with your doctor.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • If you are taking a salt substitute that has potassium, potassium-sparing diuretics, or potassium, talk with your doctor.
  • If you are on a low-salt or salt-free diet, talk with your doctor.
  • Low white blood cell counts have happened with captopril, a drug like this one. This may lead to more chance of getting an infection. Most of the time, this has happened in people with kidney problems, mainly if they have certain other health problems. Call your doctor right away if you have signs of infection like fever, chills, or sore throat. Talk with your doctor.
  • If you are taking this medicine and have high blood pressure, talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
  • Talk with your doctor before you drink alcohol.
  • Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
  • Tell your doctor if you have too much sweat, fluid loss, throwing up, or loose stools. This may lead to low blood pressure.
  • If you are taking lithium, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with Altace.
  • This medicine may not work as well in black patients. Talk with the doctor.
  • A very bad reaction called angioedema has happened with this medicine. Sometimes, this has been deadly. The chance of angioedema may be higher in black patients. Talk with the doctor.

How is this medicine (Altace) best taken?

Use Altace as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take with or without food.
  • Take this medicine at the same time of day.
  • Keep taking Altace as you have been told by your doctor or other health care provider, even if you feel well.
  • To gain the most benefit, do not miss doses.
  • Swallow whole. Do not chew, break, or crush.
  • You may sprinkle contents of capsule on applesauce or in apple juice. Do not chew.
  • You may sprinkle contents of capsule into a glass of water.
  • If needed, you can mix a dose for future use. After mixing, you may store a mixture for up to 24 hours at room temperature or up to 48 hours in the refrigerator.
  • Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.

What do I do if I miss a dose?

  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Signs of a high potassium level like a heartbeat that does not feel normal; change in thinking clearly and with logic; feeling weak, lightheaded, or dizzy; feel like passing out; numbness or tingling; or shortness of breath.
  • Very bad dizziness or passing out.
  • Cough that does not go away.
  • Very bad belly pain.
  • Very upset stomach or throwing up.
  • Liver problems have happened with drugs like this one. Sometimes, this has been deadly. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Altace (ramipril) or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Altace. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Contraindications

Altace is contraindicated in patients who are hypersensitive to this product or any other ACE inhibitor (e.g., a patient who has experienced angioedema during therapy with any other ACE inhibitor).

Altace is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer Altace within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor [see Warnings and Precautions (5.1)].

Do not co-administer Altace with aliskiren:

  • in patients with diabetes

Adverse Reactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Hypertension

Altace has been evaluated for safety in over 4000 patients with hypertension; of these, 1230 patients were studied in U.S. controlled trials, and 1107 were studied in foreign controlled trials. Almost 700 of these patients were treated for at least one year. The overall incidence of reported adverse events was similar in Altace and placebo patients. The most frequent clinical side effects (possibly or probably related to study drug) reported by patients receiving Altace in placebo-controlled trials were: headache (5.4%), dizziness (2.2%), and fatigue or asthenia (2.0%), but only the last one was more common in Altace patients than in patients given placebo. Generally the side effects were mild and transient, and there was no relation to total dosage within the range of 1.25 mg–20 mg. Discontinuation of therapy because of a side effect was required in approximately 3% of U.S. patients treated with Altace. The most common reasons for discontinuation were: cough (1.0%), dizziness (0.5%), and impotence (0.4%).

Of observed side effects considered possibly or probably related to study drug that occurred in U.S. placebo-controlled trials in more than 1% of patients treated with Altace, only asthenia (fatigue) was more common on Altace than placebo (2% [n=13/651] vs. 1% [n=2/286], respectively).

In placebo-controlled trials, there was also an excess of upper respiratory infection and flu syndrome in the Altace group, not attributed at that time to ramipril. As these studies were carried out before the relationship of cough to ACE inhibitors was recognized, some of these events may represent ramipril-induced cough. In a later 1-year study, increased cough was seen in almost 12% of Altace patients, with about 4% of patients requiring discontinuation of treatment.

Reduction in the Risk of Myocardial Infarction, Stroke, and Death from Cardiovascular Causes

HOPE Study

Safety data in the Heart Outcomes Prevention Evaluation (HOPE) study were collected as reasons for discontinuation or temporary interruption of treatment. The incidence of cough was similar to that seen in the Acute Infarction Ramipril Efficacy (AIRE) trial. The rate of angioedema was the same as in previous clinical trials [see Warnings and Precautions (5.1)].

Table 1. Reasons for Discontinuation or Temporary Interruption of TreatmentHOPE Study
Placebo
(N=4652)
Altace
(N=4645)
Discontinuation at any time 32% 34%
Permanent discontinuation 28% 29%
Reasons for stopping
  Cough 2% 7%
  Hypotension or dizziness 1.5% 1.9%
  Angioedema 0.1% 0.3%

Heart Failure Post-Myocardial Infarction

AIRE Study

Adverse reactions (except laboratory abnormalities) considered possibly/probably related to study drug that occurred in more than 1% of patients and more frequently on Altace are shown below. The incidences are from the AIRE study. The follow-up time was between 6 and 46 months for this study.

Table 2. Percentage of Patients with Adverse Events Possibly/ Probably Related to Study DrugPlacebo-Controlled (AIRE) Mortality Study
Adverse Event Placebo
(N=982)
Altace
(N=1004)
Hypotension 5% 11%
Cough increased 4% 8%
Dizziness 3% 4%
Angina pectoris 2% 3%
Nausea 1% 2%
Postural hypotension 1% 2%
Syncope 1% 2%
Vomiting 0.5% 2%
Vertigo 0.7% 2%
Abnormal kidney function 0.5% 1%
Diarrhea 0.4% 1%

Other Adverse Reactions

Other adverse reactions reported in controlled clinical trials (in less than 1% of Altace patients), or rarer events seen in post-marketing experience, include the following (in some, a causal relationship to drug is uncertain):

Body as a whole: Anaphylactoid reactions [see Warnings and Precautions (5.1)].

Cardiovascular: Symptomatic hypotension (reported in 0.5% of patients in U.S. trials) [see Warnings and Precautions (5.5)], syncope, and palpitations.

Hematologic: Pancytopenia, hemolytic anemia, and thrombocytopenia.

Decreases in hemoglobin or hematocrit (a low value and a decrease of 5 g/dL or 5%, respectively) were rare, occurring in 0.4% of patients receiving Altace alone and in 1.5% of patients receiving Altace plus a diuretic.

Renal: Acute renal failure. Some hypertensive patients with no apparent pre-existing renal disease have developed minor, usually transient, increases in blood urea nitrogen and serum creatinine when taking Altace, particularly when Altace was given concomitantly with a diuretic [see Warnings and Precautions (5.3)].

Angioneurotic edema: Angioneurotic edema has been reported in 0.3% of patients in U.S. clinical trials of Altace [see Warnings and Precautions (5.1) ].

Gastrointestinal: Hepatic failure, hepatitis, jaundice, pancreatitis, abdominal pain (sometimes with enzyme changes suggesting pancreatitis), anorexia, constipation, diarrhea, dry mouth, dyspepsia, dysphagia, gastroenteritis, increased salivation, and taste disturbance.

Dermatologic: Apparent hypersensitivity reactions (manifested by urticaria, pruritus, or rash, with or without fever), photosensitivity, purpura, onycholysis, pemphigus, pemphigoid, erythema multiforme, toxic epidermal necrolysis, and Stevens-Johnson syndrome.

Neurologic and Psychiatric: Anxiety, amnesia, convulsions, depression, hearing loss, insomnia, nervousness, neuralgia, neuropathy, paresthesia, somnolence, tinnitus, tremor, vertigo, and vision disturbances.

Miscellaneous: As with other ACE inhibitors, a symptom complex has been reported which may include a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia, fever, vasculitis, eosinophilia, photosensitivity, rash and other dermatologic manifestations. Additionally, as with other ACE inhibitors, eosinophilic pneumonitis has been reported.

Other: Arthralgia, arthritis, dyspnea, edema, epistaxis, impotence, increased sweating, malaise, myalgia, and weight gain.

Post-Marketing Experience

In addition to adverse reactions reported from clinical trials, there have been rare reports of hypoglycemia reported during Altace therapy when given to patients concomitantly taking oral hypoglycemic agents or insulin. The causal relationship is unknown.

Clinical Laboratory Test Findings

Creatinine and Blood Urea Nitrogen: Increases in creatinine levels occurred in 1.2% of patients receiving Altace alone, and in 1.5% of patients receiving Altace and a diuretic. Increases in blood urea nitrogen levels occurred in 0.5% of patients receiving Altace alone and in 3% of patients receiving Altace with a diuretic. None of these increases required discontinuation of treatment. Increases in these laboratory values are more likely to occur in patients with renal insufficiency or those pretreated with a diuretic and, based on experience with other ACE inhibitors, would be expected to be especially likely in patients with renal artery stenosis [see Warnings and Precautions (5.3)]. As ramipril decreases aldosterone secretion, elevation of serum potassium can occur. Use potassium supplements and potassium sparing diuretics with caution, and monitor the patient's serum potassium frequently [see Warnings and Precautions (5.8)].

Hemoglobin and Hematocrit: Decreases in hemoglobin or hematocrit (a low value and a decrease of 5 g/dL or 5%, respectively) were rare, occurring in 0.4% of patients receiving Altace alone and in 1.5% of patients receiving Altace plus a diuretic. No US patients discontinued treatment because of decreases in hemoglobin or hematocrit.

Other (causal relationships unknown): Clinically important changes in standard laboratory tests were rarely associated with Altace administration. Elevations of liver enzymes, serum bilirubin, uric acid, and blood glucose have been reported, as have cases of hyponatremia and scattered incidents of leucopenia, eosinophilia, and proteinuria. In US trials, less than 0.2% of patients discontinued treatment for laboratory abnormalities; all of these were cases of proteinuria or abnormal liver-function tests.

Clinical Studies

Hypertension

Altace has been compared with other ACE inhibitors, beta-blockers, and thiazide diuretics as monotherapy for hypertension. It was approximately as effective as other ACE inhibitors and as atenolol.

Administration of Altace to patients with mild to moderate hypertension results in a reduction of both supine and standing blood pressure to about the same extent with no compensatory tachycardia. Symptomatic postural hypotension is infrequent, although it can occur in patients who are salt- and/or volume-depleted [see Warnings and Precautions (5.5)]. Use of Altace in combination with thiazide diuretics gives a blood pressure lowering effect greater than that seen with either agent alone.

In single-dose studies, doses of 5 mg–20 mg of Altace lowered blood pressure within 1–2 hours, with peak reductions achieved 3–6 hours after dosing. The antihypertensive effect of a single dose persisted for 24 hours. In longer term (4–12 weeks) controlled studies, once-daily doses of 2.5 mg–10 mg were similar in their effect, lowering supine or standing systolic and diastolic blood pressures 24 hours after dosing by about 6/4 mmHg more than placebo. In comparisons of peak vs. trough effect, the trough effect represented about 50–60% of the peak response. In a titration study comparing divided (bid) vs. qd treatment, the divided regimen was superior, indicating that for some patients, the antihypertensive effect with once-daily dosing is not adequately maintained.

In most trials, the antihypertensive effect of Altace increased during the first several weeks of repeated measurements. The antihypertensive effect of Altace has been shown to continue during long-term therapy for at least 2 years. Abrupt withdrawal of Altace has not resulted in a rapid increase in blood pressure. Altace has been compared with other ACE inhibitors, beta-blockers, and thiazide diuretics. Altace was approximately as effective as other ACE inhibitors and as atenolol. In both Caucasians and Blacks, hydrochlorothiazide (25 or 50 mg) was significantly more effective than ramipril.

Altace was less effective in blacks than in Caucasians. The effectiveness of Altace was not influenced by age, sex, or weight.

In a baseline controlled study of 10 patients with mild essential hypertension, blood pressure reduction was accompanied by a 15% increase in renal blood flow. In healthy volunteers, glomerular filtration rate was unchanged.

Reduction in Risk of Myocardial Infarction, Stroke, and Death from Cardiovascular Causes

The HOPE study was a large, multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial design study conducted in 9541 patients (4645 on Altace) who were 55 years or older and considered at high risk of developing a major cardiovascular event because of a history of coronary artery disease, stroke, peripheral vascular disease, or diabetes that was accompanied by at least one other cardiovascular risk factor (hypertension, elevated total cholesterol levels, low HDL levels, cigarette smoking, or documented microalbuminuria). Patients were either normotensive or under treatment with other antihypertensive agents. Patients were excluded if they had clinical heart failure or were known to have a low ejection fraction (<0.40). This study was designed to examine the long-term (mean of 5 years) effects of Altace (10 mg orally once daily) on the combined endpoint of myocardial infarction, stroke, or death from cardiovascular causes.

The HOPE study results showed that Altace (10 mg/day) significantly reduced the rate of myocardial infarction, stroke, or death from cardiovascular causes (826/4652 vs. 651/4645, relative risk 0.78), as well as the rates of the 3 components of the combined endpoint. The relative risk of the composite outcomes in the Altace group as compared to the placebo group was 0.78% (95% confidence interval, 0.70–0.86). The effect was evident after about 1 year of treatment.

Table 3. Summary of Combined Components and EndpointsHOPE Study
Outcome Placebo
(N=4652)
n (%)
Altace
(N=4645)
n (%)
Relative Risk
(95% CI)
P-Value
Combined Endpoint
Myocardial infarction, stroke, or death from cardiovascular cause 826 (17.8%) 651 (14.0%) 0.78 (0.70–0.86)
P=0.0001
Component Endpoint
Death from cardiovascular causes 377 (8.1%) 282 (6.1%) 0.74 (0.64–0.87)
P=0.0002
Myocardial infarction 570 (12.3%) 459 (9.9%) 0.80 (0.70–0.90)
P=0.0003
Stroke 226 (4.9%) 156 (3.4%) 0.68 (0.56–0.84)
P=0.0002
Overall Mortality
Death from any cause 569 (12.2%) 482 (10.4%) 0.84 (0.75–0.95)
P=0.005

Figure 1. Kaplan-Meier Estimates of the Composite Outcome of Myocardial Infarction, Stroke, or Death from Cardiovascular Causes in the Ramipril Group and the Placebo Group

Altace was effective in different demographic subgroups (i.e., gender, age), subgroups defined by underlying disease (e.g., cardiovascular disease, hypertension), and subgroups defined by concomitant medication. There were insufficient data to determine whether or not Altace was equally effective in ethnic subgroups.

This study was designed with a prespecified substudy in diabetics with at least one other cardiovascular risk factor. Effects of Altace on the combined endpoint and its components were similar in diabetics (N=3577) to those in the overall study population.

Table 4. Summary of Combined Endpoints and Components in DiabeticsHOPE Study
Outcome Placebo
(N=1769)
n (%)
Altace
(N=1808)
n (%)
Relative Risk Reduction
(95% CI)
P-Value
Combined Endpoint
Myocardial infarction, stroke, or death from cardiovascular cause 351 (19.8%) 277 (15.3%) 0.25 (0.12–0.36)
P=0.0004
Component Endpoint
Death from cardiovascular causes 172 (9.7%) 112 (6.2%) 0.37 (0.21–0.51)
P=0.0001
Myocardial infarction 229 (12.9%) 185 (10.2%) 0.22 (0.06–0.36)
P=0.01
Stroke 108 (6.1%) 76 (4.2%) 0.33 (0.10–0.50)
P=0.007

Figure 2. The Beneficial Effect of Treatment with Altace on the Composite Outcome of Myocardial Infarction, Stroke, or Death from Cardiovascular Causes Overall and in Various Subgroups

Cerebrovascular disease was defined as stroke or transient ischemic attacks. The size of each symbol is proportional to the number of patients in each group. The dashed line indicates overall relative risk.

The benefits of Altace were observed among patients who were taking aspirin or other anti-platelet agents, beta-blockers, and lipid-lowering agents as well as diuretics and calcium channel blockers.

Heart Failure Post-Myocardial Infarction

Altace was studied in the AIRE trial. This was a multinational (mainly European) 161-center, 2006-patient, double-blind, randomized, parallel-group study comparing Altace to placebo in stable patients, 2–9 days after an acute myocardial infarction, who had shown clinical signs of congestive heart failure at any time after the myocardial infarction. Patients in severe (NYHA class IV) heart failure, patients with unstable angina, patients with heart failure of congenital or valvular etiology, and patients with contraindications to ACE inhibitors were all excluded. The majority of patients had received thrombolytic therapy at the time of the index infarction, and the average time between infarction and initiation of treatment was 5 days.

Patients randomized to Altace treatment were given an initial dose of 2.5 mg twice daily. If the initial regimen caused undue hypotension, the dose was reduced to 1.25 mg, but in either event doses were titrated upward (as tolerated) to a target regimen (achieved in 77% of patients randomized to Altace) of 5 mg twice daily. Patients were then followed for an average of 15 months, with the range of follow-up between 6 and 46 months.

The use of Altace was associated with a 27% reduction (p=0.002) in the risk of death from any cause; about 90% of the deaths that occurred were cardiovascular, mainly sudden death. The risks of progression to severe heart failure and of congestive heart failure-related hospitalization were also reduced, by 23% (p=0.017) and 26% (p=0.011), respectively. The benefits of Altace therapy were seen in both genders, and they were not affected by the exact timing of the initiation of therapy, but older patients may have had a greater benefit than those under 65. The benefits were seen in patients on (and not on) various concomitant medications. At the time of randomization these included aspirin (about 80% of patients), diuretics (about 60%), organic nitrates (about 55%), beta-blockers (about 20%), calcium channel blockers (about 15%), and digoxin (about 12%).

Altace dosing information

Usual Adult Dose for Diabetic Nephropathy:

Initial dose: 2.5 mg orally once a day for patients not receiving a diuretic
Maintenance dose: 2.5 to 20 mg/day orally in 1 to 2 divided doses

Usual Adult Dose for Hypertension:

Initial dose: 2.5 mg orally once a day for patients not receiving a diuretic
Maintenance dose: 2.5 to 20 mg/day orally in 1 to 2 divided doses

Usual Adult Dose for Congestive Heart Failure:

Initial dose: 2.5 mg orally twice a day
Maintenance dose: 5 mg orally twice a day

Usual Adult Dose for Left Ventricular Dysfunction:

Initial dose: 2.5 mg orally twice a day
Maintenance dose: 5 mg orally twice a day

Usual Adult Dose for Myocardial Infarction:

Initial dose: 2.5 mg orally twice a day
Maintenance dose: 5 mg orally twice a day

Ramipril Pregnancy Warnings

Animal studies have failed to reveal evidence of teratogenicity. In humans, use of drugs that act on the renin angiotensin system during the second and third trimesters increases fetal and neonatal morbidity and death. There are no controlled data in human pregnancy. AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details. US FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Use is contraindicated. (AU) Use is not recommended during the first trimester and is contraindicated during the second and third trimesters. (UK) This drug should not be used during pregnancy unless there are no alternatives and the benefit outweighs the risk to the fetus. (US) AU TGA pregnancy category: D US FDA pregnancy category: D Comments: Adequate methods of contraception should be encouraged.

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