NISOLDIPINE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Nisoldipine is a dihydropyridine calcium channel blocker that inhibits the influx of extracellular calcium ions into vascular smooth muscle and cardiac muscle cells, leading to vasodilation and reduced peripheral vascular resistance.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4; also undergoes ester hydrolysis and oxidation.
Excretion	Primarily hepatic metabolism; <1% excreted unchanged in urine; 70-80% excreted as metabolites in urine; 20-30% in feces.
Half-life	Terminal elimination half-life is 7-12 hours; prolonged in hepatic impairment and elderly, requiring dose adjustment.
Protein binding	>99% bound to plasma proteins, primarily albumin.
Volume of Distribution	4-6 L/kg; extensive tissue distribution with high lipophilicity.
Bioavailability	Oral: 5-8% due to extensive first-pass metabolism; lower in patients with hepatic impairment.
Onset of Action	Oral: 20-30 minutes; peak effect at 1-2 hours.
Duration of Action	8-12 hours; sustained blood pressure reduction over 24 hours with once-daily dosing.

Classification & Brands

Dosing & administration

10-40 mg orally twice daily (immediate-release) or 20-40 mg once daily (extended-release). Start at 10 mg twice daily (immediate) or 20 mg once daily (extended).

Dosage form	TABLET, EXTENDED RELEASE
Renal impairment	No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, consider starting at 10 mg twice daily (immediate) or 20 mg once daily (extended) and titrate cautiously.
Liver impairment	In Child-Pugh Class A or B, reduce dose by 50%. In Child-Pugh Class C, contraindicated or use with extreme caution; consider alternative therapy.
Pediatric use	Safety and efficacy not established. No standard pediatric dosing recommendations.
Geriatric use	Start at 10 mg twice daily (immediate) or 20 mg once daily (extended); titrate slowly due to increased risk of hypotension and falls. Monitor renal function and electrolyte status.

Use during pregnancy

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

Clinical note

Strong CYP3A4 inhibitors can significantly increase levels Can cause peripheral edema and reflex tachycardia.

Breastfeeding

Nisoldipine is excreted into human breast milk. The milk-to-plasma (M/P) ratio is not reported. A study in lactating women found that the average infant daily dose is approximately 0.3% of the maternal weight-adjusted dose, which is below the 10% threshold considered safe. However, due to limited data, caution is advised. Monitor breastfed infant for hypotension, bradycardia, and gastrointestinal disturbances.

Teratogenic Risk

Nisoldipine, a dihydropyridine calcium channel blocker, is classified as FDA Pregnancy Category C. Animal studies have shown embryotoxicity and teratogenicity at doses 5-10 times the maximum recommended human dose. In humans, first-trimester exposure is associated with a potential increased risk of congenital anomalies, particularly cardiovascular defects, although data are limited. Second and third trimester use may cause fetal hypoxia, uteroplacental hypoperfusion, and oligohydramnios due to maternal hypotension. Use only if potential benefit justifies risk.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Common Effects	Headache
Serious Effects

Absolute Contraindications

["Hypersensitivity to nisoldipine or any dihydropyridine","Concurrent use with strong CYP3A4 inducers (e.g., rifampin)","Cardiogenic shock","Unstable angina (relative)"]

Clinical Precautions

Precautions

["May cause hypotension (especially with rapid dose titration)","Peripheral edema is common","Caution in patients with heart failure or left ventricular dysfunction","Avoid grapefruit juice (inhibits CYP3A4)","May exacerbate angina in some patients (rare)","Hepatic impairment may increase drug exposure"]

Clinical Tips & Counseling

Drug interactions

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