Kenyan Health Patient Information Leaflet
Angiotensin Converting Enzyme Inhibitor [EPC]
INDICATIONS AND USAGE Hypertension Trandolapril tablets USP are indicated for the treatment of hypertension. They may be used alone or in combination with other antihypertensive medication such as hydrochlorothiazide. Heart Failure Post Myocardial Infarction or Left-Ventricular Dysfunction Post Myocardial Infarction Trandolapril tablets USP are indicated in stable patients who have evidence of left-ventricular systolic dysfunction (identified by wall motion abnormalities) or who are symptomatic from congestive heart failure within the first few days after sustaining acute myocardial infarction. Administration of trandolapril to Caucasian patients has been shown to decrease the risk of death (principally cardiovascular death) and to decrease the risk of heart failure-related hospitalization (see CLINICAL PHARMACOLOGY -Heart Failure or Left-Ventricular Dysfunction Post Myocardial Infarction for details of the survival trial).
DOSAGE AND ADMINISTRATION Hypertension The recommended initial dosage of trandolapril tablets for patients not receiving a diuretic is 1 mg once daily in non-black patients and 2 mg in black patients. Dosage should be adjusted according to the blood pressure response. Generally, dosage adjustments should be made at intervals of at least 1 week. Most patients have required dosages of 2 to 4 mg once daily. There is little clinical experience with doses above 8 mg. Patients inadequately treated with once-daily dosing at 4 mg may be treated with twice-daily dosing. If blood pressure is not adequately controlled with trandolapril tablets monotherapy, a diuretic may be added. In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally can occur following the initial dose of trandolapril tablets. To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued two to three days prior to beginning therapy with trandolapril tablets. (See WARNINGS . ) Then, if blood pressure is not controlled with trandolapril tablets alone, diuretic therapy should be resumed. If the diuretic cannot be discontinued, an initial dose of 0.5 mg trandolapril tablets should be used with careful medical supervision for several hours until blood pressure has stabilized. The dosage should subsequently be titrated (as described above) to the optimal response. (See WARNINGS , PRECAUTIONS and Drug Interactions . ) Concomitant administration of trandolapril tablets with potassium supplements, potassium salt substitutes, or potassium sparing diuretics can lead to increases of serum potassium. (See PRECAUTIONS . ) Heart Failure Post Myocardial Infarction or Left-Ventricular Dysfunction Post Myocardial Infarction The recommended starting dose is 1 mg, once daily. Following the initial dose, all patients should be titrated (as tolerated) toward a target dose of 4 mg, once daily. If a 4 mg dose is not tolerated, patients can continue therapy with the greatest tolerated dose. Dosage Adjustment in Renal Impairment or Hepatic Cirrhosis For patients with a creatinine clearance <30 mL/min. or with hepatic cirrhosis, the recommended starting dose, based on clinical and pharmacokinetic data, is 0.5 mg daily. Patients should subsequently have their dosage titrated (as described above) to the optimal response.
ADVERSE REACTIONS The safety experience in U.S. placebo-controlled trials included 1069 hypertensive patients, of whom 832 received trandolapril. Nearly 200 hypertensive patients received trandolapril for over one year in open-label trials. In controlled trials, withdrawals for adverse events were 2.1% on placebo and 1.4% on trandolapril. Adverse events considered at least possibly related to treatment occurring in 1% of trandolapril-treated patients and more common on trandolapril than placebo, pooled for all doses, are shown below, together with the frequency of discontinuation of treatment because of these events. ADVERSE EVENTS IN PLACEBO-CONTROLLED HYPERTENSION TRIALS Occurring at 1% or greater TRANDOLAPRIL (N=832) % Incidence (% Discontinuance) PLACEBO (N=237) % Incidence (% Discontinuance) Cough 1.9 (0.1) 0.4 (0.4) Dizziness 1.3 (0.2) 0.4 (0.4) Diarrhea 1 (0) 0.4 (0) Headache and fatigue were all seen in more than 1% of trandolapril-treated patients but were more frequently seen on placebo. Adverse events were not usually persistent or difficult to manage. Left Ventricular Dysfunction Post Myocardial Infarction Adverse reactions related to trandolapril occurring at a rate greater than that observed in placebo-treated patients with left ventricular dysfunction, are shown below. The incidences represent the experiences from the TRACE study. The follow-up time was between 24 and 50 months for this study. Percentage of Patients with Adverse Events Greater Than Placebo Placebo-Controlled (TRACE) Mortality Study Adverse Event Trandolapril N=876 Placebo N=873 Cough 35 22 Dizziness 23 17 Hypotension 11 6.8 Elevated serum uric acid 15 13 Elevated BUN 9 7.6 PICA or CABG 7.3 6.1 Dyspepsia 6.4 6 Syncope 5.9 3.3 Hyperkalemia 5.3 2.8 Bradycardia 4.7 4.4 Hypocalcemia 4.7 3.9 Myalgia 4.7 3.1 Elevated creatinine 4.7 2.4 Gastritis 4.2 3.6 Cardiogenic shock 3.8 < 2 Intermittent claudication 3.8 < 2 Stroke 3.3 3.2 Asthenia 3.3 2.6 Clinical adverse experiences possibly or probably related or of uncertain relationship to therapy occurring in 0.3% to 1% (except as noted) of the patients treated with trandolapril (with or without concomitant calcium ion antagonist or diuretic) in controlled or uncontrolled trials (N=1134) and less frequent, clinically significant events seen in clinical trials or post-marketing experience include (listed by body system): General Body Function Chest pain. Cardiovascular AV first degree block, bradycardia, edema, flushing, and palpitations. Central Nervous System Drowsiness, insomnia, paresthesia, vertigo. Dermatologic Pruritus, rash, pemphigus. Eye, Ear, Nose, Throat Epistaxis, throat inflammation, upper respiratory tract infection. Emotional, Mental, Sexual States Anxiety, impotence, decreased libido. Gastrointestinal Abdominal distention, abdominal pain/cramps, constipation, dyspepsia, diarrhea, vomiting, nausea. Hemopoietic Decreased leukocytes, decreased neutrophils. Metabolism and Endocrine Increased liver enzymes including SGPT (ALT). Musculoskeletal System Extremity pain, muscle cramps, gout. Pulmonary Dyspnea. Postmarketing The following adverse reactions were identified during post approval use of trandolapril. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. General Body Function Malaise, fever. Cardiovascular Myocardial infarction, myocardial ischemia, angina pectoris, cardiac failure, ventricular tachycardia, tachycardia, transient ischemic attack, arrhythmia. Central Nervous System Cerebral hemorrhage. Dermatologic Alopecia, sweating, Stevens-Johnson syndrome and toxic epidermal necrolysis. Emotional, Mental, Sexual States Hallucination, depression. Gastrointestinal Dry mouth, pancreatitis, jaundice and hepatitis. Hemopoietic Agranulocytosis, pancytopenia. Metabolism and Endocrine Increased SGOT (AST). Pulmonary Bronchitis. Renal and Urinary Renal failure. Clinical Laboratory Test Findings Hematology Thrombocytopenia. Serum Electrolytes Hyponatremia. Creatinine and Blood Urea Nitrogen Increases in creatinine levels occurred in 1.1% of patients receiving trandolapril alone and 7.3% of patients treated with trandolapril, a calcium ion antagonist and a diuretic. Increases in blood urea nitrogen levels occurred in 0.6% of patients receiving trandolapril alone and 1.4% of patients receiving trandolapril, a calcium ion antagonist, and 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 PRECAUTIONS and WARNINGS . ) Liver Function Tests Occasional elevation of transaminases at the rate of 3X upper normals occurred in 0.8% of patients and persistent increase in bilirubin occurred in 0.2% of patients. Discontinuation for elevated liver enzymes occurred in 0.2% of patients. Other Another potentially important adverse experience, eosinophilic pneumonitis, has been attributed to other ACE inhibitors.
HOW SUPPLIED Trandolapril tablets USP are supplied as follows: Trandolapril Tablets USP 1 mg are salmon colored, round, biconvex, uncoated tablets debossed with āEā on upper side of the bisector line on one side and ā35ā on the other side. Bottles of 100 NDC 57237-089-01 Trandolapril Tablets USP 2 mg are yellow colored, round, biconvex, uncoated tablets debossed with āEā on one side and ā36ā on the other side. Bottles of 100 NDC 57237-090-01 Trandolapril Tablets USP 4 mg are rose colored, round, biconvex, uncoated tablets debossed with āEā on one side and ā37ā on the other side. Bottles of 100 NDC 57237-091-01 Dispense in well-closed container with safety closure. Store at 20Ā° to 25Ā°C (68Ā° to 77Ā°F); excursions permitted to 15Ā° to 30Ā°C (59Ā° to 86Ā°F) [see USP Controlled Room Temperature]. Distributed by: Rising Health, LLC Saddle Brook, NJ 07663 Made in India Code: TS/DRUGS/19/1993 Revised: 01/2018