Introduction
Felodipine is a second-generation dihydropyridine calcium channel blocker (CCB) used primarily in the management of hypertension. As a selective vascular smooth muscle relaxant, it produces potent peripheral vasodilation with minimal effects on cardiac contractility or conduction. First approved by the FDA in 1991, felodipine remains an important therapeutic option in cardiovascular medicine, particularly available in extended-release formulations that provide 24-hour blood pressure control with once-daily dosing.
Mechanism of Action
Felodipine exerts its pharmacological effects by selectively blocking L-type calcium channels in vascular smooth muscle cells. This inhibition prevents calcium influx through voltage-dependent channels, resulting in relaxation of arterial smooth muscle and subsequent reduction in peripheral vascular resistance. The drug demonstrates particular selectivity for vascular tissue over cardiac muscle, resulting in potent vasodilation with minimal negative inotropic effects. Unlike non-dihydropyridine calcium channel blockers, felodipine has negligible effects on AV node conduction and SA node automaticity.
Indications
- Hypertension: Management of essential hypertension, either as monotherapy or in combination with other antihypertensive agents
- Off-label: Raynaud's phenomenon (limited evidence)
- Note: Unlike some other calcium channel blockers, felodipine is not indicated for angina pectoris
Dosage and Administration
Standard dosing:- Initial dose: 2.5-5 mg once daily
- Maintenance dose: 2.5-10 mg once daily
- Maximum dose: 10 mg daily (some sources suggest 20 mg daily in resistant cases)
- Geriatric patients: Initiate with 2.5 mg daily due to increased bioavailability
- Hepatic impairment: Start with 2.5 mg daily; use with caution
- Renal impairment: No dosage adjustment typically needed
- Administration: Swallow extended-release tablets whole; do not crush or chew
Pharmacokinetics
Absorption: Well absorbed orally but undergoes extensive first-pass metabolism (~15% bioavailability); extended-release formulation provides gradual absorption Distribution: Highly protein-bound (>99%); volume of distribution approximately 10 L/kg Metabolism: Extensive hepatic metabolism via CYP3A4; no active metabolites Elimination: Primarily renal excretion (70%) as metabolites; fecal excretion (10%); elimination half-life 11-16 hours Onset/Duration: Gradual onset with peak effect at 2.5-5 hours; duration 24 hoursContraindications
- Hypersensitivity to felodipine or other dihydropyridines
- Severe hypotension
- Cardiogenic shock
- Acute myocardial infarction with hemodynamic instability
Warnings and Precautions
- Peripheral edema: Dose-dependent, occurs in 10-15% of patients
- Hypotension: May cause symptomatic hypotension, particularly in volume-depleted patients
- Reflex tachycardia: May occur, especially with rapid dose escalation
- Hepatic impairment: Requires dose reduction and careful monitoring
- Heart failure: Use with caution in patients with heart failure
- Gingival hyperplasia: May occur with long-term use (monitor dental health)
Drug Interactions
Major interactions:- CYP3A4 inhibitors: Ketoconazole, itraconazole, erythromycin, clarithromycin, grapefruit juice (↑ felodipine levels)
- CYP3A4 inducers: Rifampin, carbamazepine, phenytoin (↓ felodipine levels)
- Other antihypertensives: Additive hypotensive effects
- Beta-blockers: May potentiate hypotension and reflex tachycardia
- Grapefruit juice may increase bioavailability up to 2-fold (avoid concomitant use)
- Monitor closely when adding or discontinuing CYP3A4 modulators
Adverse Effects
Common (≥5%):- Peripheral edema (dose-dependent)
- Headache
- Dizziness
- Flushing
- Fatigue
- Palpitations
- Nausea
- Abdominal discomfort
- Gingival hyperplasia
- Severe hypotension
- Syncope
- Myocardial ischemia (rare)
- Allergic reactions
- Elevated liver enzymes
Monitoring Parameters
- Blood pressure (standing and supine) at initiation and periodically
- Heart rate
- Signs/symptoms of peripheral edema
- Liver function tests (baseline and periodically)
- Renal function
- Dental examination for gingival changes
- Symptoms of hypotension (dizziness, syncope)
Patient Education
- Take medication at the same time each day, with or without food
- Swallow extended-release tablets whole; do not crush or chew
- Avoid grapefruit and grapefruit juice during therapy
- Rise slowly from sitting/lying position to prevent dizziness
- Monitor for swelling in ankles/feet and report significant edema
- Maintain good oral hygiene and regular dental check-ups
- Do not discontinue abruptly; consult provider for dose adjustments
- Report symptoms of low blood pressure (dizziness, lightheadedness, fainting)
- Inform all healthcare providers of felodipine use before starting new medications
References
1. Micromedex® Solutions. Felodipine monograph. Truven Health Analytics. 2023. 2. Lexicomp Online®. Felodipine drug information. Wolters Kluwer. 2023. 3. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. JNC 8 Guidelines. JAMA. 2014. 4. Pfizer Laboratories. Plendil® (felodipine) prescribing information. 2022. 5. Moffett BS, et al. Calcium Channel Blockers. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023. 6. Epstein BJ, et al. Dihydropyridine calcium channel antagonists in the management of hypertension. Drugs. 2007. 7. Meredith PA, Elliott HL. Felodipine: pharmacokinetics and pharmacodynamics in patients with hypertension. Pharmacol Ther. 1991.