INSPRA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INSPRA (INSPRA).
Selective aldosterone receptor antagonist that competitively inhibits aldosterone binding at mineralocorticoid receptors, reducing sodium reabsorption and potassium excretion in the distal nephron, and decreasing cardiac and vascular fibrosis.
| Metabolism | Primarily hepatic via CYP3A4; metabolites are inactive. No significant metabolism via other CYP isoforms. |
| Excretion | Approximately 67% of the dose is excreted in the urine as metabolites, with less than 5% as unchanged drug. About 32% is excreted in the feces via biliary elimination. |
| Half-life | The terminal elimination half-life is approximately 3-6 hours in healthy subjects, but may be prolonged to up to 10 hours in patients with moderate hepatic impairment (Child-Pugh Class B). |
| Protein binding | Eplerenone is approximately 50% bound to plasma proteins, primarily alpha-1-acid glycoprotein. |
| Volume of Distribution | The apparent volume of distribution is approximately 0.6-0.7 L/kg, suggesting distribution into total body water. |
| Bioavailability | The absolute bioavailability of eplerenone is 69% after oral administration. Food does not affect the bioavailability. |
| Onset of Action | Following oral administration, the antihypertensive effect begins within 1-2 weeks, with maximal effect reached after 4 weeks of dosing. |
| Duration of Action | The duration of action is approximately 24 hours, allowing once-daily dosing. The blood pressure-lowering effect is maintained over the dosing interval. |
Initial: 25 mg orally once daily, titrated to 50 mg once daily within 4 weeks as tolerated. Maximum: 50 mg daily.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-49 mL/min: Initiate at 25 mg every other day. eGFR <30 mL/min: Not recommended. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: 25 mg once daily initially. Child-Pugh Class C: Not studied; avoid use. |
| Pediatric use | Not approved for pediatric patients; safety and efficacy not established. |
| Geriatric use | Initiate at 25 mg once daily; titrate cautiously due to age-related renal impairment. Monitor potassium and renal function closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INSPRA (INSPRA).
| Breastfeeding | Not recommended. No data on excretion in human milk; animal studies show eplerenone present in rat milk with a milk-to-plasma ratio of approximately 0.5. Potential for adverse effects in nursing infant (e.g., hyperkalemia). |
| Teratogenic Risk | Pregnancy Category B. No evidence of teratogenicity in animal studies at doses up to 1000 mg/kg/day (rat) and 450 mg/kg/day (rabbit). However, use during pregnancy only if clearly needed; limited human data. Theoretical risk of hyperkalemia in fetus due to maternal aldosterone blockade. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Serum potassium >5.5 mEq/L at initiation","Severe renal impairment (CrCl <30 mL/min)","Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir)"]
| Precautions | ["Hyperkalemia risk, especially in patients with renal impairment, diabetes, or those taking potassium supplements or other potassium-sparing diuretics","Monitor serum potassium and renal function frequently during therapy"] |
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| Fetal Monitoring |
| Monitor maternal serum potassium and renal function regularly; consider fetal ultrasound to assess growth if used in pregnancy due to limited safety data. |
| Fertility Effects | No evidence of impaired fertility in animal studies at doses up to 1000 mg/kg/day (rat). Human data not available. |