TRANDOLAPRIL

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

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.

What the body does with it

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

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

NSAIDs may diminish the antihypertensive effect Lithium levels may be increased Risk of angioedema can occur at any time discontinue immediately.

Breastfeeding	No human data on transfer into breast milk. M/P ratio unknown. Due to potential for neonatal hypotension and renal impairment, use is not recommended during breastfeeding. Alternative antihypertensives with more safety data are preferred.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Common Effects	heart failure
Serious Effects

Absolute Contraindications

["Hypersensitivity to trandolapril or any ACE inhibitor","History of angioedema related to previous ACE inhibitor therapy","Pregnancy (avoid, especially second and third trimesters)","Concomitant use with aliskiren in patients with diabetes mellitus or renal impairment (GFR < 60 mL/min)"]

Clinical Precautions

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)"]

Clinical Tips & Counseling

Drug interactions

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