Felodipine extended-release tablets are indicated for the treatment of hypertension.

Felodipine extended-release tablets may be used alone or concomitantly with other antihypertensive agents.

The recommended starting dose is 5 mg once a day. Depending on the patient's response, the dosage can be decreased to 2.5 mg or increased to 10 mg once a day. These adjustments should occur generally at intervals of not less than 2 weeks. The recommended dosage range is 2.5 mg to 10 mg once daily. In clinical trials, doses above 10 mg daily showed an increased blood pressure response but a large increase in the rate of peripheral edema and other vasodilatory adverse events (see ADVERSE REACTIONS). Modification of the recommended dosage is usually not required in patients with renal impairment.

Felodipine extended-release tablets should regularly be taken either without food or with a light meal (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism). Felodipine extended-release tablets should be swallowed whole and not crushed or chewed.

Patients over 65 years of age are likely to develop higher plasma concentrations of felodipine (see CLINICAL PHARMACOLOGY). In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range (2.5 mg daily). Elderly patients should have their blood pressure closely monitored during any dosage adjustment.

Patients  with  Impaired  Liver  Function

Patients with impaired liver function may have elevated plasma concentrations of felodipine and may respond to lower doses of felodipine extended-release tablets; therefore, patients should have their blood pressure monitored closely during dosage adjustment of felodipine extended-release tablets (see CLINICAL PHARMACOLOGY).

Felodipine extended-release tablets are contraindicated in patients who are hypersensitive to this product.

General

Hypotension

Felodipine, like other calcium antagonists, may occasionally precipitate significant hypotension and, rarely, syncope. It may lead to reflex tachycardia which in susceptible individuals may precipitate angina pectoris. (See ADVERSE REACTIONS.)

Heart Failure

Although acute hemodynamic studies in a small number of patients with NYHA Class II or III heart failure treated with felodipine have not demonstrated negative inotropic effects, safety in patients with heart failure has not been established. Caution, therefore, should be exercised when using felodipine extended-release in patients with heart failure or compromised ventricular function, particularly in combination with a beta-blocker.

Patients with Impaired Liver Function

Patients with impaired liver function may have elevated plasma concentrations of felodipine and may respond to lower doses of felodipine extended-release; therefore, a starting dose of 2.5 mg once a day is recommended. These patients should have their blood pressure monitored closely during dosage adjustment of felodipine extended-release. (See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION.)

Peripheral Edema

Peripheral edema, generally mild and not associated with generalized fluid retention, was the most common adverse event in the clinical trials. The incidence of peripheral edema was both dose and age dependent. Frequency of peripheral edema ranged from about 10% in patients under 50 years of age taking 5 mg daily to about 30% in those over 60 years of age taking 20 mg daily. This adverse effect generally occurs within 2 to 3 weeks of the initiation of treatment.

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)

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:

Body  as  a  Whole: Chest pain, facial edema, flu-like illness

Cardiovascular:  Myocardial infarction, hypotension, syncope, angina pectoris, arrhythmia, tachycardia, premature beats

Digestive: Abdominal pain, diarrhea, vomiting, dry mouth, flatulence, acid regurgitation

Endocrine: Gynecomastia

Hematologic:  Anemia

Metabolic: ALT (SGPT) increased

Musculoskeletal: Arthralgia, back pain, leg pain, foot pain, muscle cramps, myalgia, arm pain, knee pain, hip pain

Nervous/Psychiatric: Insomnia, depression, anxiety disorders, irritability, nervousness, somnolence, decreased libido

Respiratory: Dyspnea, pharyngitis, bronchitis, influenza, sinusitis, epistaxis, respiratory infection

Skin:  Angioedema, contusion, erythema, urticaria, leukocytoclastic  vasculitis

Special  Senses: Visual disturbances

Urogenital: Impotence, urinary frequency, urinary urgency, dysuria, polyuria.

Gingival  Hyperplasia: 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.)

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.

General

Hypotension

Felodipine, like other calcium antagonists, may occasionally precipitate significant hypotension and, rarely, syncope. It may lead to reflex tachycardia which in susceptible individuals may precipitate angina pectoris. (See ADVERSE REACTIONS.)

Heart Failure

Although acute hemodynamic studies in a small number of patients with NYHA Class II or III heart failure treated with felodipine have not demonstrated negative inotropic effects, safety in patients with heart failure has not been established. Caution, therefore, should be exercised when using felodipine extended-release in patients with heart failure or compromised ventricular function, particularly in combination with a beta-blocker.

Patients with Impaired Liver Function

Patients with impaired liver function may have elevated plasma concentrations of felodipine and may respond to lower doses of felodipine extended-release; therefore, a starting dose of 2.5 mg once a day is recommended. These patients should have their blood pressure monitored closely during dosage adjustment of felodipine extended-release. (See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION.)

Peripheral Edema

Peripheral edema, generally mild and not associated with generalized fluid retention, was the most common adverse event in the clinical trials. The incidence of peripheral edema was both dose and age dependent. Frequency of peripheral edema ranged from about 10% in patients under 50 years of age taking 5 mg daily to about 30% in those over 60 years of age taking 20 mg daily. This adverse effect generally occurs within 2 to 3 weeks of the initiation of treatment.