Lotensin (Benazepril Hydrochloride) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

Lotensin has been evaluated for safety in over 6000 patients with hypertension; over 700 of these patients were treated for at least one year. The overall incidence of reported adverse events was comparable in Lotensin and placebo patients.

The reported side effects were generally mild and transient, and there was no relation between side effects and age, duration of therapy, or total dosage within the range of 2 to 80 mg. Discontinuation of therapy because of a side effect was required in approximately 5% of U.S. patients treated with Lotensin and in 3% of patients treated with placebo.

The most common reasons for discontinuation were headache (0.6%) and cough (0.5%) (see PRECAUTIONS, Cough).

The 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 Lotensin are shown below.

PATIENTS IN U.S. PLACEBO-CONTROLLED STUDIES

	LOTENSIN (N=964)		PLACEBO (N=496)
	N	%	N	%
Headache	60	6.2	21	4.2
Dizziness	35	3.6	12	2.4
Fatigue	23	2.4	11	2.2
Somnolence	15	1.6	2	0.4
Postural Dizziness	14	1.5	1	0.2
Nausea	13	1.3	5	1.0
Cough	12	1.2	5	1.0

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

Cardiovascular: Symptomatic hypotension was seen in 0.3% of patients, postural hypotension in 0.4%, and syncope in 0.1%; these reactions led to discontinuation of therapy in 4 patients who had received benazepril monotherapy and in 9 patients who had received benazepril with hydrochlorothiazide (see PRECAUTIONS and WARNINGS). Other reports included angina pectoris, palpitations, and peripheral edema.

Renal: Of hypertensive patients with no apparent preexisting renal disease, about 2% have sustained increases in serum creatinine to at least 150% of their baseline values while receiving Lotensin, but most of these increases have disappeared despite continuing treatment. A much smaller fraction of these patients (less than 0.1%) developed simultaneous (usually transient) increases in blood urea nitrogen and serum creatinine.

Fetal/Neonatal Morbidity and Mortality: See WARNINGS, Fetal/Neonatal Morbidity and Mortality.

Angioedema: Angioedema has been reported in patients receiving ACE inhibitors. During clinical trials in hypertensive patients with benazepril, 0.5% of patients experienced edema of the lips or face without other manifestations of angioedema. Angioedema associated with laryngeal edema and/or shock may be fatal. If angioedema of the face, extremities, lips, tongue, or glottis and/or larynx occurs, treatment with Lotensin should be discontinued and appropriate therapy instituted immediately (see WARNINGS).

Dermatologic: Stevens-Johnson syndrome, pemphigus, apparent hypersensitivity reactions (manifested by dermatitis, pruritus, or rash), photosensitivity, and flushing.

Gastrointestinal: Pancreatitis, constipation, gastritis, vomiting, and melena.

Hematologic: Thrombocytopenia and hemolytic anemia.

Neurologic and Psychiatric: Anxiety, decreased libido, hypertonia, insomnia, nervousness, and paresthesia.

Other: Asthma, bronchitis, dyspnea, sinusitus, urinary tract infection, infection, arthritis, impotence, alopecia, arthralgia, myalgia, asthenia, and sweating.

Another potentially important adverse experience, eosinophilic pneumonitis, has been attributed to other ACE inhibitors.

Pediatric Patients: The adverse experience profile for pediatric patients appears to be similar to that seen in adult patients. Infants below the age of 1 year should not be given ACE inhibitors due to concerns over possible effects on kidney development.

The long-term effects of benazepril on growth and development have not been studied.

Clinical Laboratory Test Findings

Creatinine and Blood Urea Nitrogen: Of hypertensive patients with no apparent preexisting renal disease, about 2% have sustained increases in serum creatinine to at least 150% of their baseline values while receiving Lotensin, but most of these increases have disappeared despite continuing treatment. A much smaller fraction of these patients (less than 0.1%) developed simultaneous (usually transient) increases in blood urea nitrogen and serum creatinine. 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 PRECAUTIONS, General).

Potassium: Since benazepril 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 PRECAUTIONS).

Hemoglobin: Decreases in hemoglobin (a low value and a decrease of 5 g/dL) were rare, occurring in only 1 of 2,014 patients receiving Lotensin alone and in 1 of 1,357 patients receiving Lotensin plus a diuretic. No U.S. patients discontinued treatment because of decreases in hemoglobin.

Other (causal relationships unknown): Clinically important changes in standard laboratory tests were rarely associated with Lotensin administration. Elevations of uric acid, blood glucose, serum bilirubin, and liver enzymes (see WARNINGS) have been reported, as have scattered incidents of hyponatremia, electrocardiographic changes, leukopenia, eosinophilia, and proteinuria. In U.S. trials, less than 0.5% of patients discontinued treatment because of laboratory abnormalities.

REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO LOTENSIN

Possible Lotensin side effects / adverse reactions in 61 year old female

Reported by a physician from United States on 2007-02-06

Patient: 61 year old female weighing 111.0 kg (244.2 pounds)

Reactions: Back Pain, Drooling, Aphasia, Cerebrovascular Accident, Fall, Dysarthria, Limb Injury, Hypoaesthesia Facial, Hypertension

Adverse event resulted in: hospitalization

Suspect drug(s):
Lotensin
    Dosage: 5 mg, qd
    Indication: Hypertension
    Start date: 1986-01-01

Lotensin
    Dosage: 10 mg, qd

Lotensin
    Dosage: 20 mg, bid
    Start date: 2004-01-01

Other drugs received by patient: Synthroid

Possible Lotensin side effects / adverse reactions in 64 year old male

Reported by a physician from United States on 2007-02-13

Patient: 64 year old male

Reactions: Urinary Tract Obstruction, Blood Creatine Phosphokinase Increased, Renal Failure, Rhabdomyolysis, Urinary Tract Infection, Hepatic Failure

Adverse event resulted in: hospitalization

Suspect drug(s):
Crestor
    Administration route: Oral

Casodex
    Administration route: Oral

Coumadin

Norvasc

Lotensin

Floxmax

Possible Lotensin side effects / adverse reactions in 57 year old female

Reported by a individual with unspecified qualification from United States on 2007-02-20

Patient: 57 year old female

Reactions: LIP Swelling

Suspect drug(s):
Lotensin

Possible Lotensin side effects / adverse reactions in 28 year old female

Reported by a consumer/non-health professional from China on 2007-03-08

Patient: 28 year old female

Reactions: Normal Newborn, Caesarean Section, Drug Exposure During Pregnancy

Suspect drug(s):
Lotensin

Possible Lotensin side effects / adverse reactions in 68 year old male

Reported by a physician from China on 2007-06-08

Patient: 68 year old male weighing 55.0 kg (121.0 pounds)

Reactions: Musculoskeletal Stiffness, Gait Disturbance

Adverse event resulted in: disablity

Suspect drug(s):
Lotensin

Possible Lotensin side effects / adverse reactions in 64 year old male

Reported by a health professional (non-physician/pharmacist) from United States on 2007-06-25

Patient: 64 year old male weighing 74.4 kg (163.7 pounds)

Reactions: Angioedema

Adverse event resulted in: hospitalization

Suspect drug(s):
Lotensin

Possible Lotensin side effects / adverse reactions in 72 year old male

Reported by a pharmacist from United States on 2007-06-26

Patient: 72 year old male weighing 88.0 kg (193.6 pounds)

Reactions: Pneumonia, Angioedema, Myocardial Infarction, Cardiac Failure Congestive

Adverse event resulted in: hospitalization

Suspect drug(s):
Lotensin

Possible Lotensin side effects / adverse reactions in 77 year old male

Reported by a health professional (non-physician/pharmacist) from United States on 2007-06-27

Patient: 77 year old male weighing 70.7 kg (155.5 pounds)

Reactions: Angioedema, Swollen Tongue, Oedema Mouth

Adverse event resulted in: hospitalization

Suspect drug(s):
Lotensin

Possible Lotensin side effects / adverse reactions in 49 year old male

Reported by a consumer/non-health professional from China on 2007-07-16

Patient: 49 year old male

Reactions: Blood Bilirubin Increased, Gamma-Glutamyltransferase Increased, Aspartate Aminotransferase Increased, Alanine Aminotransferase Increased, Urine Protein/creatinine Ratio Increased, Urine Bilirubin Increased

Suspect drug(s):
Lotensin

Other drugs received by patient: Adalat

Possible Lotensin side effects / adverse reactions in 68 year old male

Reported by a physician from China on 2007-07-19

Patient: 68 year old male weighing 55.0 kg (121.0 pounds)

Reactions: Musculoskeletal Stiffness, Gait Disturbance

Adverse event resulted in: disablity

Suspect drug(s):
Lotensin

Possible Lotensin side effects / adverse reactions in 65 year old male

Reported by a physician from United States on 2007-10-08

Patient: 65 year old male weighing 98.9 kg (217.5 pounds)

Reactions: Pharyngeal Oedema, Tongue Oedema, Stent Placement, Coronary Artery Disease, Percutaneous Coronary Intervention, Myocardial Infarction

Suspect drug(s):
Lotensin
    Dosage: 40 mg, bid
    Administration route: Oral
    Indication: Hypertension
    Start date: 1987-01-01

Benazepril Hydrochloride
    Dosage: 40 mg, bid
    Administration route: Oral
    Indication: Hypertension
    End date: 2007-09-12

Other drugs received by patient: Glucovance; Byetta; Actos; Levemir; Valium; Plavix; Lipitor; Hydrochlorothiazide; Potassium Chloride; Bisoprolol Fumarate

Possible Lotensin side effects / adverse reactions in 38 year old male

Reported by a consumer/non-health professional from China on 2007-10-16

Patient: 38 year old male

Reactions: Heart Rate Decreased

Suspect drug(s):
Lotensin

Other drugs received by patient: Aspirin; JIN KUI Shen QI Pill

Possible Lotensin side effects / adverse reactions in 59 year old female

Reported by a individual with unspecified qualification from United States on 2007-10-23

Patient: 59 year old female

Reactions: White Blood Cell Count Decreased, Palpitations, Chest Pain, Proteinuria, Microalbuminuria, Asthenia, Pain in JAW

Suspect drug(s):
Lotensin
    Dosage: 40 mg, qd
    Administration route: Oral
    Indication: Hypertension
    Start date: 2007-02-23

Lotrel
    Dosage: unk, qd
    Administration route: Oral
    Indication: Hypertension
    Start date: 2007-09-01
    End date: 2007-09-01

Other drugs received by patient: Aspirin; Humalog; Vytorin; Lantus

Possible Lotensin side effects / adverse reactions in 87 year old male

Reported by a physician from China on 2007-10-24

Patient: 87 year old male weighing 50.0 kg (110.0 pounds)

Reactions: Peripheral Coldness, Cyanosis, Rash Papular, Raynaud's Phenomenon, Erythema

Adverse event resulted in: hospitalization

Suspect drug(s):
Lotensin

Other drugs received by patient: Asmeton; Amiodarone