ALTACE has been evaluated for safety in over 4,000 patients with hypertension; of these, 1,230 patients were studied in US controlled trials, and 1,107 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 US placebo-controlled trials were: headache (5.4%), “dizziness” (2.2%) and fatigue or asthenia (2.0%), but only the last 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 to 20 mg. Discontinuation of therapy because of a side effect was required in approximately 3% of US 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 US placebo-controlled trials in more than 1% of patients treated with ALTACE, only asthenia (fatigue) was more common on Altace than placebo (2% vs. 1%).
PATIENTS IN US PLACEBO CONTROLLED STUDIES
| ALTACE || Placebo |
| (n=651) || (n=286) |
|n ||% ||n ||% |
|Asthenia (Fatigue) ||13 ||2 ||2 ||1 |
In placebo-controlled trials, there was also an excess of upper respiratory infection and flu syndrome in the ramipril 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 ramipril patients, with about 4% of patients requiring discontinuation of treatment.
Heart Failure Post Myocardial Infarction
Adverse reactions (except laboratory abnormalities) considered possibly/probably related to study drug that occurred in more than one percent of patients and more frequently on ramipril are shown below. The incidences represent the experiences from the AIRE study. The follow-up time was between 6 and 46 months for this study.
Percentage of Patients with Adverse Events Possibly/ Probably Related to Study Drug
Placebo-Controlled (AIRE) Mortality Study
| (n=1004) || (n=982) |
|Hypotension ||11 ||5 |
|Cough Increased ||8 ||4 |
|Dizziness ||4 ||3 |
|Angina Pectoris ||3 ||2 |
|Nausea ||2 ||1 |
|Postural Hypotension ||2 ||1 |
|Syncope ||2 ||1 |
|Vomiting ||2 ||0.5 |
|Vertigo ||2 ||0.7 |
|Abnormal Kidney Function ||1 ||0.5 |
|Diarrhea ||1 ||0.4 |
Safety data in the HOPE trial were collected as reasons for discontinuation or temporary interruption of treatment. The incidence of cough was similar to that seen in the AIRE trial. The rate of angioedema was the same as in previous clinical trials (see WARNINGS).
| RAMIPRIL || PLACEBO |
| (N=4645) || (N=4652) |
|% ||% |
|Discontinuation at any time ||34 ||32 |
|Permanent discontinuation ||29 ||28 |
|Reasons for stopping Cough ||7 ||2 |
|Hypotension or Dizziness ||1.9 ||1.5 |
|Angioedema ||0.3 ||0.1 |
Other adverse experiences reported in controlled clinical trials (in less than 1% of ramipril patients), or rarer events seen in postmarketing experience, include the following (in some, a causal relationship to drug use is uncertain):
Body As a Whole: Anaphylactoid reactions. (See WARNINGS.)
Cardiovascular: Symptomatic hypotension (reported in 0.5% of patients in US trials) (See WARNINGS and PRECAUTIONS), syncope and palpitations.
Hematologic: Pancytopenia, hemolytic anemia and thrombocytopenia.
Renal: 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.) Acute renal failure.
Angioneurotic Edema: Angioneurotic edema has been reported in 0.3% of patients in US clinical trials. (See WARNINGS.)
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.
Fetal/Neonatal Morbidity and Mortality. See WARNINGS: Fetal/Neonatal Morbidity and Mortality.
Other: arthralgia, arthritis, dyspnea, edema, epistaxis, impotence, increased sweating, malaise, myalgia, and weight gain.
Post-Marketing Experience: In addition to adverse events 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.) Since ramipril decreases aldosterone secretion, elevation of serum potassium can occur. Potassium supplements and potassium-sparing diuretics should be given with caution, and the patient’s serum potassium should be monitored frequently. (See WARNINGS and PRECAUTIONS.)
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 leukopenia, 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.
REPORTS OF SUSPECTED ALTACE SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Altace. The information is not vetted and should not be considered as verified clinical evidence.
Possible Altace side effects / adverse reactions in 85 year old female
Reported by a physician from France on 2011-10-05
Patient: 85 year old female
Reactions: Leukocytoclastic Vasculitis, Skin Ulcer, Dermatitis Bullous, Rash, Cutaneous Lupus Erythematosus
Possible Altace side effects / adverse reactions in 69 year old female
Reported by a pharmacist from Italy on 2011-10-11
Patient: 69 year old female
Reactions: Hyperkalaemia, Blood Potassium Increased, Blood Glucose Abnormal, Renal Failure Acute
Adverse event resulted in: hospitalization
Other drugs received by patient: Solosa; Metformin HCL; Lercanidipine; Lyrica; Lucen; Atenolol
Possible Altace side effects / adverse reactions in 80 year old male
Reported by a consumer/non-health professional from France on 2011-10-11
Patient: 80 year old male
Reactions: Angioedema, Motor Dysfunction, LIP Oedema, Cerebrovascular Disorder
Adverse event resulted in: hospitalization
Dosage: 1 df, qd
Administration route: Oral
Dosage: 1 df, qd
Administration route: Oral
Dosage: 72 mg, single
Start date: 2011-09-02
Other drugs received by patient: Metformin Hydrochloride; Umuline