LEXXEL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LEXXEL (LEXXEL).
LEXXEL is a combination of felodipine, a dihydropyridine calcium channel blocker that inhibits calcium influx into vascular smooth muscle and cardiac muscle, causing vasodilation and reduced myocardial contractility, and enalapril, an angiotensin-converting enzyme (ACE) inhibitor that prevents conversion of angiotensin I to angiotensin II, reducing vasoconstriction, aldosterone secretion, and sodium reabsorption.
| Metabolism | Felodipine is extensively metabolized by CYP3A4; enalapril is hydrolyzed to enalaprilat, which is not further metabolized. |
| Excretion | Renal: ~35-50% as unchanged drug (enalaprilat), biliary/fecal: ~15-30% as metabolites and unchanged drug; total renal elimination of enalaprilat accounts for ~60-80% of dose. |
| Half-life | Enalapril: ~1.3 hours; Enalaprilat: terminal half-life ~35-38 hours, with multiple-dose accumulation half-life ~11 hours; effective half-life for ACE inhibition ~24 hours. |
| Protein binding | Enalapril: ~50-60% bound to plasma proteins; Enalaprilat: ~50-60% bound, primarily to albumin and other proteins. |
| Volume of Distribution | Enalaprilat: ~1.1-1.6 L/kg; indicates extensive extravascular distribution; Vd increases with heart failure. |
| Bioavailability | Enalapril: oral bioavailability ~60-70% (range 40-80%), converted to active enalaprilat; food does not significantly affect absorption. |
| Onset of Action | Oral: 1-2 hours for peak enalaprilat concentrations; antihypertensive effect begins within 2-4 hours, peak effect at 4-8 hours. |
| Duration of Action | Antihypertensive effect persists for 24 hours with once-daily dosing; longer duration in combination with hydrochlorothiazide; dose-dependent up to 24-36 hours. |
1 tablet (felodipine 5 mg / enalapril 5 mg) orally once daily, may increase to 2 tablets once daily after 2-4 weeks if needed.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR 30-60 mL/min: initial dose 1 tablet once daily; GFR <30 mL/min: not recommended due to enalapril accumulation. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: initial dose 1 tablet once daily; Child-Pugh C: contraindicated. |
| Pediatric use | Not established; safety and efficacy in pediatric patients have not been studied. |
| Geriatric use | Start at 1 tablet once daily; monitor blood pressure and renal function closely due to increased sensitivity to hypotensive effects and potential for renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LEXXEL (LEXXEL).
| Breastfeeding | Enalapril: Excreted in breast milk in low concentrations (M/P ratio ~0.3); risk of hypotension in neonates. Felodipine: Excreted in milk (M/P ratio unknown); limited data. Avoid use during breastfeeding or monitor infant for adverse effects. |
| Teratogenic Risk | First trimester: Risk based on ACE inhibitor component (enalapril) - associated with increased risk of congenital malformations (cardiovascular, CNS) if used in first trimester. Second and third trimesters: Known fetotoxicity (oligohydramnios, neonatal renal failure, skull hypoplasia, hypotension). Fetal risks from felodipine: Limited human data; animal studies show fetotoxicity at high doses. Overall, LEXXEL is contraindicated in pregnancy. |
■ FDA Black Box Warning
Use in pregnancy: Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as pregnancy is detected.
| Serious Effects |
["Hypersensitivity to felodipine, enalapril, or any ACE inhibitor","History of angioedema related to previous ACE inhibitor therapy","Hereditary or idiopathic angioedema","Pregnancy"]
| Precautions | ["Fetal toxicity","Hypotension","Angioedema","Hepatic impairment","Renal impairment","Hyperkalemia","Aortic stenosis","CHF patients","Cough","Drug interactions (e.g., CYP3A4 inhibitors/inducers, NSAIDs)"] |
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| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, BUN), electrolytes (potassium) and fetal ultrasound for oligohydramnios, growth restriction, and skull ossification if inadvertent exposure. Serial fetal monitoring in second/third trimester. |
| Fertility Effects | Enalapril: No known adverse effects on fertility. Felodipine: No known adverse effects. No clinical data on combination. |