ISRADIPINE
Clinical safety rating
cautionComprehensive clinical and safety monograph for ISRADIPINE (ISRADIPINE).
Isradipine is a dihydropyridine calcium channel blocker that inhibits the influx of extracellular calcium ions into vascular smooth muscle and myocardial cells via L-type calcium channels, leading to vasodilation and reduced peripheral vascular resistance, with minimal negative inotropic effect.
| Metabolism | Hepatic metabolism via CYP3A4 isoenzyme; undergoes extensive first-pass metabolism. |
| Excretion | Renal: 65% (as metabolites, <1% unchanged); Fecal: 35% (biliary elimination); total clearance 1.4 L/min. |
| Half-life | Terminal elimination half-life 8 hours (range 6-12 hours); clinical context: supports twice-daily dosing, requires dose adjustment in hepatic impairment. |
| Protein binding | 96%, primarily to alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | 2.9 L/kg (3-5 L/kg reported); clinical meaning: extensive tissue distribution, high affinity for vascular smooth muscle. |
| Bioavailability | Oral: 15-24% (first-pass effect); sustained-release: approximately 30% due to reduced presystemic metabolism. |
| Onset of Action | Oral: 20-30 minutes (immediate-release); sustained-release: 2 hours. |
| Duration of Action | Immediate-release: 6-8 hours; sustained-release: 12-24 hours; clinical note: sustained-release formulation provides consistent blood pressure control over 24 hours. |
| Molecular Weight | 371.47 |
2.5-10 mg orally twice daily. Initial dose: 2.5 mg twice daily, titrate to 5-10 mg twice daily as needed.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR >30 mL/min). For severe renal impairment (GFR <30 mL/min), initiate at 2.5 mg twice daily and titrate cautiously. |
| Liver impairment | For Child-Pugh Class A or B: initiate at 2.5 mg twice daily and titrate cautiously. For Child-Pugh Class C: use isradipine with caution; consider starting at 2.5 mg once daily and adjust based on response and tolerability. |
| Pediatric use | Not FDA-approved for pediatric use. Limited data: initial dose 0.05-0.15 mg/kg orally 3-4 times daily; maximum 0.8 mg/kg/day. |
| Geriatric use | Initiate at 2.5 mg twice daily; titrate slowly due to increased risk of hypotension. Maximum dose usually 5 mg twice daily. |
| 1st trimester | Avoid; potential teratogenicity in animal studies. Use only if benefit outweighs risk. |
| 2nd trimester | Caution; may cause maternal hypotension and reduce uteroplacental perfusion. Use only if clearly needed. |
| 3rd trimester | Caution; risk of fetal hypoxia and neonatal hypotension. Avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for ISRADIPINE (ISRADIPINE).
| Placental transfer | Crosses placenta; evidence from animal and human studies demonstrates transfer to fetal circulation. |
| Breastfeeding | Isradipine is excreted into breast milk in small amounts. Limited data suggest no adverse effects in infants, but caution is advised. Monitor infant for hypotension. |
| Lactation Rating | L3: Limited data - possibly safe |
| Teratogenic Risk | Isradipine is a pregnancy category C drug. In animal studies, it caused embryotoxicity, fetotoxicity, and teratogenicity (skeletal anomalies) at doses 2-3 times the maximum recommended human dose. There are no adequate and well-controlled studies in pregnant women. Use only if potential benefit justifies potential risk. First trimester: potential for teratogenic effects. Second and third trimesters: may cause fetal hypoxia, IUGR, and preterm delivery due to maternal hypotension; also associated with decreased uterine blood flow. |
| Fetal Monitoring | Monitor maternal blood pressure frequently, especially at dose initiation and titration. Assess fetal heart rate and uterine activity, particularly in preeclampsia therapy. Consider ultrasound monitoring for fetal growth if used long-term. Monitor for maternal hypotension, reflex tachycardia, and peripheral edema. |
| Fertility Effects | Isradipine has been shown to reduce fertility in animal studies (decreased pregnancy rates, increased preimplantation loss) at doses comparable to human therapeutic doses. In humans, calcium channel blockers may impair sperm motility and function, potentially reducing male fertility. Effects on female fertility are unknown but theoretical interference with oocyte maturation or implantation exists. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to isradipine or dihydropyridine derivativesSevere aortic stenosisCardiogenic shockUnstable anginaAcute myocardial infarction (within 4 weeks)
| Precautions | May cause hypotension, peripheral edema, heart failure exacerbation (particularly in patients with pre-existing left ventricular dysfunction), and increased angina or myocardial infarction upon abrupt withdrawal. Use caution in patients with aortic stenosis, hepatic impairment, and in elderly patients. May cause gingival hyperplasia. Should be used with caution in patients with severe left ventricular dysfunction or heart failure. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they inhibit CYP3A4 and can increase isradipine levels, leading to toxicity. High-fat meals may slow absorption but do not significantly alter overall effect. No other specific dietary restrictions. |
| Clinical Pearls | Isradipine is a dihydropyridine calcium channel blocker with high vascular selectivity; it causes less negative inotropic effect than nifedipine. It is used for hypertension and has been studied for Parkinson's disease but not FDA-approved for that indication. Its short half-life (8 hours) necessitates twice-daily dosing. Monitor for peripheral edema, headache, and dizziness. Avoid grapefruit juice as it increases drug levels. Use with caution in patients with aortic stenosis or heart failure with reduced ejection fraction. |
| Patient Advice | Take this medication exactly as prescribed, usually twice daily. · Do not drink grapefruit juice while taking isradipine. · Avoid sudden discontinuation; consult your doctor before stopping. · Common side effects include swelling of ankles/feet, headache, and dizziness; report severe or persistent symptoms. · This medicine does not cure hypertension but helps control it; continue taking even if you feel well. |
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