FELODIPINE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Felodipine is a dihydropyridine calcium channel blocker that inhibits the influx of calcium ions across cardiac and smooth muscle cells, leading to vasodilation and reduced peripheral vascular resistance, thereby lowering blood pressure.

What the body does with it

Metabolism	Hepatic metabolism primarily via cytochrome P450 3A4 (CYP3A4) to inactive metabolites.
Excretion	Felodipine is extensively metabolized in the liver via CYP3A4, with no significant renal excretion of unchanged drug. Approximately 70% of the dose is excreted in urine as inactive metabolites, and about 10% is eliminated in feces. Biliary excretion accounts for a minor fraction.
Half-life	The terminal elimination half-life is approximately 11 to 16 hours in healthy adults. This supports once-daily dosing for sustained antihypertensive effect, though steady-state is reached after 5-7 days.
Protein binding	Approximately 99% bound to plasma proteins, primarily albumin and to a lesser extent alpha-1-acid glycoprotein.
Volume of Distribution	The volume of distribution is about 10 L/kg, indicating extensive tissue distribution. This large Vd reflects high lipophilicity and binding to vascular smooth muscle.
Bioavailability	Oral extended-release: approximately 15-20% due to extensive first-pass metabolism. Food can increase bioavailability by up to 30%, while grapefruit juice significantly increases it via CYP3A4 inhibition.
Onset of Action	Oral immediate-release: 2 to 5 hours for a measurable decrease in blood pressure. Extended-release: onset is gradual, with initial effects within 2-4 hours, but full effect may require 2-4 weeks of therapy.
Duration of Action	Extended-release formulations provide antihypertensive coverage for 24 hours. Immediate-release duration is shorter, typically less than 8 hours, and is not recommended for chronic therapy due to potential for reflex tachycardia.

Classification & Brands

Dosing & administration

5-10 mg orally once daily, starting at 5 mg and titrating as needed. Maximum 10 mg/day.

Dosage form	TABLET, EXTENDED RELEASE
Renal impairment	No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, caution advised with starting dose of 2.5 mg orally once daily.
Liver impairment	Child-Pugh Class A: No adjustment. Child-Pugh Class B: Initial dose 2.5 mg orally once daily; titrate cautiously. Child-Pugh Class C: Avoid use or use with extreme caution, consider alternative.
Pediatric use	Not FDA-approved for pediatric use. Off-label: For hypertension, starting dose 2.5 mg orally once daily in children ≥6 years, titrate to max 10 mg/day. Weight-based data insufficient.
Geriatric use	Initial dose 2.5 mg orally once daily, titrate slowly due to increased bioavailability and sensitivity. Maximum 10 mg/day.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Strong CYP3A4 inhibitors (eg ketoconazole) can significantly increase levels Can cause peripheral edema and gingival hyperplasia.

Breastfeeding	Felodipine is excreted into human milk; estimated infant dose is 0.5-1.6% of maternal weight-adjusted dose. M/P ratio not reported. Use with caution; monitor infant for hypotension and bradycardia.
Teratogenic Risk	First trimester: Limited human data; animal studies show no teratogenicity at clinically relevant doses. Second and third trimesters: Risk of fetal hypotension and hypoxia; may cause decreased placental perfusion. Potential for neonatal toxicity (hypotension, bradycardia) if used near delivery.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Common Effects	Peripheral edema
Serious Effects

Absolute Contraindications

Hypersensitivity to felodipine or any component of the formulation; caution in patients with aortic stenosis or severe left ventricular outflow obstruction.

Clinical Precautions

Precautions

Beta-blocker withdrawal may exacerbate angina; caution in heart failure with reduced ejection fraction (NYHA III/IV), severe hypotension, hepatic impairment, elderly patients, and concomitant use of CYP3A4 inhibitors or inducers.

Clinical Tips & Counseling

Drug interactions

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