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. |
| Molecular Weight | Benazepril: 424.49 Da; Felodipine: 384.25 Da |
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 | Contraindicated in first trimester due to risk of fetotoxicity from benazepril (ACE inhibitor) and potential antifertility effects from felodipine. |
| 2nd trimester | Contraindicated in second trimester due to ACE inhibitor association with oligohydramnios, fetal renal dysfunction, and skull ossification defects. |
| 3rd trimester | Contraindicated in third trimester because of ACE inhibitor-induced oligohydramnios, neonatal renal failure, and hypotension; felodipine may cause uteroplacental hypoperfusion. |
Clinical note
Comprehensive clinical and safety monograph for LEXXEL (LEXXEL).
| Placental transfer | Benazepril and felodipine cross the placenta; benazeprilat levels in fetal plasma are approximately 10-20% of maternal levels. Felodipine shows significant placental transfer in animal studies. |
| Breastfeeding | Benazeprilat (active metabolite) is excreted in breast milk in low concentrations; felodipine is also excreted in milk. Theoretical risk of neonatal hypotension and renal impairment. Use alternative antihypertensives if possible. Monitor infant for hypotension and feeding difficulties. |
■ 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 |
PregnancyHistory of angioedema with prior ACE inhibitorKnown hypersensitivity to benazepril or felodipineSevere aortic stenosisBilateral renal artery stenosis
| Precautions | Fetal toxicity, Hypotension, Angioedema, Hepatic impairment, Renal impairment, Hyperkalemia, Aortic stenosis, CHF patients, Cough, Drug interactions (e.g., CYP3A4 inhibitors/inducers, NSAIDs) |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they increase felodipine levels. Avoid high-salt foods to minimize edema. No other significant food interactions. |
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| Lactation Rating | L4 (Limited data - potential adverse effects) or 'Avoid'. |
| 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. |
| 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. |
| Clinical Pearls | LEXXEL is a combination of enalapril (ACE inhibitor) and felodipine (calcium channel blocker). Avoid use in pregnancy due to risk of fetal harm. Monitor renal function and serum potassium, as ACE inhibitors may cause hyperkalemia. Felodipine may cause peripheral edema, which can be minimized by reducing salt intake. Both drugs are metabolized by CYP3A4; avoid grapefruit juice as it inhibits CYP3A4 and increases felodipine levels. Use caution in patients with severe aortic stenosis or renal artery stenosis. |
| Patient Advice | Take exactly as prescribed, usually once daily without food (grapefruit juice) and with a full glass of water. · Avoid grapefruit juice while taking this medication as it can increase side effects. · Notify your doctor if you become pregnant or plan to become pregnant; this drug can harm an unborn baby. · Do not stop taking suddenly; abrupt discontinuation may worsen chest pain or increase blood pressure. · Report any swelling of the hands/ankles/feet (edema), persistent cough, or signs of high potassium (e.g., muscle weakness, irregular heartbeat). · If you have diabetes or kidney problems, regular monitoring of blood potassium and kidney function is needed. |