TRANDOLAPRIL
Clinical safety rating: avoid
Contraindicated (not allowed)
Trandolapril is a prodrug that is hydrolyzed to its active metabolite trandolaprilat, which inhibits angiotensin-converting enzyme (ACE), blocking the conversion of angiotensin I to angiotensin II. This reduces vasoconstriction, aldosterone secretion, and sodium reabsorption, leading to decreased blood pressure and preload/afterload reduction.
| Metabolism | Prodrug trandolapril is hydrolyzed by esterases to active trandolaprilat. Trandolaprilat is further glucuronidated and excreted mainly in urine and feces. Minimal CYP450 involvement. |
| Excretion | Renal: 33% (as trandolaprilat); Fecal: 66% (as trandolapril and trandolaprilat); Biliary: minimal |
| Half-life | Trandolapril: 6 hours; Trandolaprilat: 24 hours (terminal); effective half-life for ACE inhibition: ~24 hours allowing once-daily dosing |
| Protein binding | Trandolapril: 80% (primarily albumin); Trandolaprilat: 65-94% (concentration-dependent) |
| Volume of Distribution | Trandolapril: ~2.2 L/kg; Trandolaprilat: ~0.7 L/kg; extensive tissue distribution |
| Bioavailability | Oral: 40-60% (trandolapril); rapidly converted to active trandolaprilat (bioavailability of active drug is 10-15%) |
| Onset of Action | Oral: 1-2 hours for peak ACE inhibition; antihypertensive effect within 2-4 hours |
| Duration of Action | >24 hours; once-daily dosing provides 24-hour blood pressure control |
| Molecular Weight | 430.5 |
1–2 mg orally once daily; maximum 4 mg once daily.
| Dosage form | TABLET |
| Renal impairment | GFR <30 mL/min: 0.5 mg orally once daily; maximum 1 mg daily. GFR 30–60 mL/min: 0.5 mg orally once daily; maximum 2 mg daily. Hemodialysis: 0.5 mg orally once daily; administer after dialysis. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: 0.5 mg orally once daily; maximum 1 mg daily. Child-Pugh C: not recommended. |
| Pediatric use | Not established for children <18 years; safety and efficacy not established. |
| Geriatric use | Initiate at 0.5 mg orally once daily; titrate slowly due to increased risk of hypotension and renal impairment. |
| 1st trimester | Contraindicated: associated with teratogenicity including fetal renal dysfunction and oligohydramnios. |
| 2nd trimester | Contraindicated: risk of fetal renal dysfunction, oligohydramnios, and neonatal renal failure. |
| 3rd trimester | Contraindicated: risk of fetal renal dysfunction, oligohydramnios, and neonatal renal failure. |
Clinical note
NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Risk of angioedema can occur at any time discontinue immediately.
| Placental transfer | Crosses placental barrier; detected in fetal serum and amniotic fluid. |
| Breastfeeding | Trandolapril is excreted into breast milk in low amounts; however, due to potential for adverse effects on the infant's renin-angiotensin system, it is generally not recommended during breastfeeding. Use alternative antihypertensive agents if possible. |
■ FDA Black Box Warning
Fetal toxicity: Use during pregnancy can cause oligohydramnios, fetal renal dysfunction, skull hypoplasia, and death. Discontinue as soon as pregnancy is detected.
| Common Effects | heart failure |
| Serious Effects |
History of angioedema related to previous ACE inhibitor therapyHereditary or idiopathic angioedemaPregnancy (second and third trimesters)Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min/1.73 m²)Severe renal impairment (GFR < 30 mL/min/1.73 m²)Hyperkalemia (> 5.5 mEq/L) unresponsive to therapy
| Precautions | Angioedema (risk higher in black patients), Hypotension (especially in volume/salt-depleted patients), Renal impairment (monitor renal function), Hyperkalemia (avoid with potassium-sparing diuretics), Cough (most common side effect), Hepatic failure (rare), Neutropenia/agranulocytosis (rare, higher risk with renal impairment/collagen vascular disease) |
Loading safety data…
| Lactation Rating | L3 (Moderately safe) - limited data; risk of infant hypotension and renal impairment. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show fetotoxicity. Second and third trimesters: Known to cause oligohydramnios, fetal renal dysfunction, skull ossification defects, and neonatal hypotension. Contraindicated in pregnancy, especially after 20 weeks gestation due to risk of fetal renin-angiotensin system blockade. |
| Fetal Monitoring | Maternal: Monitor blood pressure, renal function (serum creatinine, BUN), and electrolytes. Fetal: Serial ultrasound for amniotic fluid volume and fetal renal function if inadvertent exposure in second/third trimester. Neonatal: Monitor for hypotension and hyperkalemia after delivery. |
| Fertility Effects | No known direct effects on human fertility. Animal studies showed no impairment of fertility. However, use in pregnancy is contraindicated; women of childbearing potential should use effective contraception. |
| Food/Dietary |
| Avoid high-potassium foods (e.g., bananas, oranges, spinach, salt substitutes) unless instructed. Limit alcohol intake as it may enhance hypotensive effects. |
| Clinical Pearls | Monitor renal function and serum potassium 1–2 weeks after initiation and with dose increases. Ensure patient is not volume-depleted before starting. Cough incidence is lower than other ACE inhibitors due to prolonged ACE inhibition; still possible. Use with caution in patients with bilateral renal artery stenosis. Can cause angioedema; risk increased in black patients. |
| Patient Advice | Report any swelling of face, lips, or throat immediately. · Avoid salt substitutes containing potassium. · Do not stop taking without consulting your doctor. · Take at the same time each day, with or without food. · May cause dizziness; avoid driving until you know how it affects you. |