TECZEM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TECZEM (TECZEM).
Enalapril inhibits angiotensin-converting enzyme (ACE), reducing angiotensin II formation, leading to vasodilation and decreased aldosterone secretion. Diltiazem inhibits calcium ion influx across cardiac and smooth muscle cells, causing coronary vasodilation and decreased myocardial contractility.
| Metabolism | Enalapril is hydrolyzed to active enalaprilat, mainly hepatically. Diltiazem is extensively metabolized in the liver via CYP3A4. |
| Excretion | Renal: 40-50% unchanged; hepatic/biliary/fecal: 50-60% as metabolites. |
| Half-life | Terminal elimination half-life: 3-4 hours for diltiazem; clinical context: requires twice-daily dosing due to short half-life. |
| Protein binding | 70-80% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 5-7 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: 35-60% due to first-pass metabolism; IV: 100%. |
| Onset of Action | Oral: 30-60 minutes; IV: 2-5 minutes. |
| Duration of Action | Oral: 6-8 hours; IV: 1-3 hours; clinical notes: extended-release formulations provide 12-24 hour coverage. |
1 to 2 tablets (enalapril 5 mg/diltiazem 180 mg) orally once daily. Maximum: 2 tablets daily.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR >30 mL/min: No adjustment. GFR 10-30 mL/min: Use with caution, monitor potassium and creatinine. GFR <10 mL/min: Avoid use. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Use with caution, consider starting at lowest dose. Child-Pugh C: Contraindicated. |
| Pediatric use | Safety and efficacy not established for patients <18 years. |
| Geriatric use | Start at lowest dose, monitor renal function and electrolytes due to age-related decreased renal function and increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TECZEM (TECZEM).
| Breastfeeding | Enalapril is excreted in human milk in trace amounts; the M/P ratio is approximately 0.01. Felodipine is excreted in human milk; the M/P ratio is unknown. Due to potential for adverse effects in the nursing infant, especially renal effects from enalapril, breastfeeding is not recommended during TECZEM therapy. |
| Teratogenic Risk | TECZEM (enalapril maleate and felodipine) is contraindicated in pregnancy. ACE inhibitors can cause fetal and neonatal morbidity and death when administered to pregnant women. First trimester exposure may be associated with a small increased risk of congenital anomalies; second and third trimester exposure is associated with oligohydramnios, fetal renal dysfunction, skull ossification defects, and neonatal hypotension, anuria, and renal failure. Felodipine: No teratogenic effects in animal studies at clinically relevant doses; however, limited human data. Combined use should be avoided in pregnancy. |
■ FDA Black Box Warning
Use in pregnancy: ACE inhibitors can cause injury and death to the developing fetus. Discontinue as soon as possible when pregnancy is detected.
| Serious Effects |
["Hypersensitivity to enalapril, diltiazem, or any component","History of angioedema related to ACE inhibitors","Second- or third-degree AV block (except with pacemaker)","Sick sinus syndrome","Severe hypotension","Cardiogenic shock","Concurrent use with riociguat"]
| Precautions | ["Hypotension","Angioedema","Hepatic injury","Heart block","Bradycardia","Renal impairment","Hyperkalemia"] |
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| Fetal Monitoring | Monitor maternal blood pressure, renal function (serum creatinine, BUN), and serum electrolytes regularly. Assess fetal well-being with ultrasound if pregnancy is suspected. In case of inadvertent exposure, perform fetal ultrasound to assess amniotic fluid volume and renal function. |
| Fertility Effects | Enalapril: No significant effects on fertility in animal studies. Felodipine: No impairment of fertility in rats at clinically relevant doses. No human data on fertility effects; however, calcium channel blockers may affect sperm function theoretically. |