Dosing and uses of Lexxel (enalapril/felodipine)
Adult dosage forms and strengths
enalapril/felodipine
tablet
- 5mg/5mg
LEXXEL (enalapril maleate-felodipine ER) is a combination product, consisting of an outer layer of enalapril maleate surrounding a core tablet of an extended-release felodipine formulation
Hypertension
Not indicated for initial therapy
Usual dose: enalapril maleate 5 mg/felodipine 5 mg PO qd
Increase to enalapril maleate 10 mg/felodipine 10 mg PO qD if needed after 1-2 week
If control remains unsatisfactory, consider addition of thiazide diuretic
Renal Impairment
Use caution in patients with impaired renal function
Other Information
When LEXXEL is taken with food, the peak concentration of felodipine is almost doubled, and the trough (24-hour) concentration is approximately halved
Felodipine component of LEXXEL has not been shown to be bioequivalent to the available extended-release felodipine
Pediatric dosage forms and strengths
<18 years: Safety/efficacy not established
Lexxel (enalapril/felodipine) adverse (side) effects
1-10%
EnalapriL
- Chest pain
- Cough
- Dizziness
- Headache
- Hypotension
- Rash
Felodipine
- Cough
- Dizziness
- Headache
- Flushing
- Palpitations
- Peripheral edema
Frequency not defined
EnalapriL
- Asthenia
- Hyperkalemia
- Nausea
- Vomiting
Felodipine
- Gingival hyperplasia
- Rash
- Tachycardia
- Upper respiratory infection
Warnings
Black box warnings
Enalapril: Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death
Contraindications
Hypersensitivity to either component or sulfonamides
History of angioedema
Hereditary or idiopathic angioedema
Bilateral renal artery stenosis
Pregnancy (2nd and 3rd trimesters): significant risk of fetal and neonatal morbidity and mortality
Cautions
CHF, aortic stenosis, hypotension (initially or after dose increases)
Persistent progressive dermatologic reactions
Exacerbation of angina (during initiation of treatment, after dose increase, or withdrawal of beta blocker)
Liver impairment
Avoid taking with grapefruit juice
Heart failure or compromised ventricular function
Excessive hypotension if concomitant diuretics, hypovolemia, hyponatremia
Risk of hyperkalemia, especially in patients with renal impairment, DM or those taking concomitant K+-elevating drugs
Aheresis (LDL) with dextran sulfate
Hypertrophic cardiomyopathy, collagen vascular disease, hemodialysis with high flux membrane, renal or arotic stenosis
Pregnancy and lactation
Pregnancy category: C (1st trimester); D (2nd & 3rd trimester)
Lactation: excreted in breast milk, use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Lexxel (enalapril/felodipine)
Half-Life
enalapril: parent drug 1.3 hr, active metabolite (enalaprilat) 11 hr
felodipine: 10-16 hr
Absorption
enalapril 60% bioavailability
felodipine 20% bioavailability
Onset
enalapril: initial 1-4 hr, peak 8-18 hr
felodipine: 2-5 hr
Duration
enalapril: 12-24 hr
felodipine: 24 hr
Peak Plasma Time
enalapril: 1 hr
felodipine: 2-5 hr
Protein Bound
enalapril: 50-60%
felodipine: 99%
Metabolism
enalapril: liver (70%)
enalapril undergoes hepatic biotransformation to enalaprilat within 4 hr
felodipine: hepatic P450 enzyme CYP3A4
Metabolites: enalaprilat (active)
felodipine: pyridine analog (inactive)
Clearance
enalapril: renal 158 mL/min
felodipine: 823 mL/min
Excretion
felodipine: urine 37% feces 10%
Dialyzable
enalapril HD: yes
felodipine HD: no
Mechanism of action
Lexxel is a fixed-combination tablet that combines an angiotensin-converting enzyme (ACE) inhibitor, enalapril, and a calcium channel blocker, felodipine
Enalapril is a prodrug hydrolyzed in vivo to enalaprilat; enalaprilat prevents conversion of angiotensin I to angiotensin II (a potent vasoconstrictor) through competitive inhibition of angiotensin coverting enzyme (ACE) resulting in decreased plasma angiotensin II concentrations and consequently, blood pressure may be reduced in part through decreased vasoconstriction, increase renin activity, and decrease aldosterone secretion
Felodipine, a channel blocker: inhibits transmembrane influx of extracellular Ca ions across myocardial and vascular smooth muscle cell membranes, without changing serum calcium concentrations, resulting in inhibition of cardiac and vascular smooth muscle contraction, thereby dilating main coronary and systemic arteries
