adverse reactions
ADVERSE REACTIONS In controlled studies in the United States and overseas, approximately 3,000 patients were treated with felodipine as either the extended-release or the immediate-release formulation. The most common clinical adverse events reported with felodipine extended-release administered as monotherapy at the recommended dosage range of 2.5 mg to 10 mg once a day were peripheral edema and headache. Peripheral edema was generally mild, but it was age and dose related and resulted in discontinuation of therapy in about 3% of the enrolled patients. Discontinuation of therapy due to any clinical adverse event occurred in about 6% of the patients receiving felodipine extended-release, principally for peripheral edema, headache, or flushing. Adverse events that occurred with an incidence of 1.5% or greater at any of the recommended doses of 2.5 mg to 10 mg once a day (felodipine extended-release, N = 861; Placebo, N = 334), without regard to causality, are compared to placebo and are listed by dose in the table below. These events are reported from controlled clinical trials with patients who were randomized to a fixed dose of felodipine extended-release tablets or titrated from an initial dose of 2.5 mg or 5 mg once a day. A dose of 20 mg once a day has been evaluated in some clinical studies. Although the antihypertensive effect of felodipine extended-release tablets is increased at 20 mg once a day, there is a disproportionate increase in adverse events, especially those associated with vasodilatory effects (see DOSAGE AND ADMINISTRATION). Percent of Patients with Adverse Events in Controlled Trials* of Felodipine Extended-Release (N = 861) as Monotherapy without Regard to Causality (Incidence of discontinuations shown in parentheses) Body System Adverse Events Placebo N = 334 2.5 mg N = 255 5 mg N = 581 10 mg N = 408 Body as a Whole Peripheral Edema 3.3 (0) 2 (0) 8.8 (2.2) 17.4 (2.5) Asthenia 3.3 (0) 3.9 (0) 3.3 (0) 2.2 (0) Warm Sensation 0 (0) 0 (0) 0.9 (0.2) 1.5 (0) Cardiovascular Palpitation 2.4 (0) 0.4 (0) 1.4 (0.3) 2.5 (0.5) Digestive Nausea 1.5 (0.9) 1.2 (0) 1.7 (0.3) 1 (0.7) Dyspepsia 1.2 (0) 3.9 (0) 0.7 (0) 0.5 (0) Constipation 0.9 (0) 1.2 (0) 0.3 (0) 1.5 (0.2) Nervous Headache 10.2 (0.9) 10.6 (0.4) 11 (1.7) 14.7 (2) Dizziness 2.7 (0.3) 2.7 (0) 3.6 (0.5) 3.7 (0.5) Paresthesia 1.5 (0.3) 1.6 (0) 1.2 (0) 1.2 (0.2) Respiratory Upper Respiratory Infection 1.8 (0) 3.9 (0) 1.9 (0) 0.7 (0) Cough 0.3 (0) 0.8 (0) 1.2 (0) 1.7 (0) Rhinorrhea 0 (0) 1.6 (0) 0.2 (0) 0.2 (0) Sneezing 0 (0) 1.6 (0) 0 (0) 0 (0) Skin Rash 0.9 (0) 2 (0) 0.2 (0) 0.2 (0) Flushing 0.9 (0.3) 3.9 (0) 5.3 (0.7) 6.9 (1.2) Patients in titration studies may have been exposed to more than one dose level of felodipine extended-release tablets. * Adverse events that occurred in 0.5% up to 1.5% of patients who received felodipine extended-release in all controlled clinical trials at the recommended dosage range of 2.5 mg to 10 mg once a day, and serious adverse events that occurred at a lower rate, or events reported during marketing experience (those lower rate events are in italics) are listed below. These events are listed in order of decreasing severity within each category, and the relationship of these events to administration of felodipine extended-release is uncertain: Chest pain, facial edema, flu-like illness Body as a Whole: , , , , , tachycardia, premature beats Cardiovascular: Myocardial infarction hypotension syncope angina pectoris arrhythmia Abdominal pain, diarrhea, vomiting, dry mouth, flatulence, acid regurgitation Digestive: Gynecomastia Endocrine: Hematologic: Anemia ALT (SGPT) increased Metabolic: Arthralgia, back pain, leg pain, foot pain, muscle cramps, myalgia, arm pain, knee pain, hip pain Musculoskeletal: Insomnia, depression, anxiety disorders, irritability, nervousness, somnolence, decreased libido Nervous/Psychiatric: Dyspnea, pharyngitis, bronchitis, influenza, sinusitis, epistaxis, respiratory infection Respiratory: , contusion, erythema, urticaria, Skin: Angioedema leukocytoclastic vasculitis Visual disturbances Special Senses: Impotence, urinary frequency, urinary urgency, dysuria, polyuria. Urogenital: Gingival hyperplasia, usually mild, occurred in < 0.5% of patients in controlled studies. This condition may be avoided or may regress with improved dental hygiene. (See PRECAUTIONS: Information for Patients.) Gingival Hyperplasia: Clinical Laboratory Test Findings Serum Electrolytes No significant effects on serum electrolytes were observed during short- and long-term therapy (see CLINICAL PHARMACOLOGY: Renal/Endocrine Effects). Serum Glucose No significant effects on fasting serum glucose were observed in patients treated with felodipine extended-release in the U.S. controlled study. Liver Enzymes One of two episodes of elevated serum transaminases decreased once drug was discontinued in clinical studies; no follow-up was available for the other patient.