TARKA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TARKA (TARKA).
Combination of trandolapril (angiotensin-converting enzyme inhibitor) and verapamil (calcium channel blocker). Trandolapril inhibits ACE, reducing angiotensin II production, leading to vasodilation and decreased aldosterone secretion. Verapamil blocks L-type calcium channels, causing coronary and peripheral vasodilation, and negative chronotropic/inotropic effects.
| Metabolism | Trandolapril is hydrolyzed to its active metabolite trandolaprilat; primarily hepatic (esterases). Verapamil undergoes extensive hepatic metabolism via CYP3A4, with multiple metabolites. Both are excreted renally. |
| Excretion | Renal: trandolaprilat 33% (unchanged 13%), trandolapril 10%; fecal: 66% (trandolaprilat 21%, trandolapril 33%); verapamil: renal 70% (16% unchanged), fecal 16% |
| Half-life | Trandolaprilat terminal t1/2 16–24 h (prolonged in renal impairment, e.g., CrCl <30 mL/min ~36 h); verapamil t1/2 6–12 h (active metabolite norverapamil t1/2 ~12 h) |
| Protein binding | Trandolapril ~80% (mainly albumin); trandolaprilat 90–94% (albumin); verapamil 90% (albumin) |
| Volume of Distribution | Trandolapril: about 0.7 L/kg (extensive tissue penetration); trandolaprilat: similar; verapamil: 4.5 L/kg (high tissue binding, e.g., heart, liver) |
| Bioavailability | Trandolapril: ~40–60% (active metabolite trandolaprilat formed via hepatic esterases; food reduces rate but not extent); verapamil: 20–35% (extensive first-pass metabolism) |
| Onset of Action | Oral: antihypertensive effect begins within 1–2 h for both components |
| Duration of Action | Trandolapril: 24 h (once-daily dosing; sustained ACE inhibition over 24 h); verapamil: 12–24 h (immediate-release verapamil alone ~8–12 h, but extended-release formulation contributes to 24 h efficacy) |
Tarka (trandolapril/verapamil) is available as fixed-dose combinations: 1 mg/180 mg, 2 mg/180 mg, 2 mg/240 mg, 4 mg/240 mg. For hypertension, initial dose is 1 mg/180 mg orally once daily; titrate based on blood pressure response, maximum dose 8 mg/480 mg per day.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | For GFR <30 mL/min/1.73 m²: not recommended. For GFR 30-60 mL/min/1.73 m²: use with caution; starting dose should be reduced (e.g., trandolapril component). No specific dose for Tarka; consider individual components. Verapamil should be used with caution; dose adjustment may be needed. |
| Liver impairment | For Child-Pugh Class A (mild): reduce dose of trandolapril; for Class B (moderate): contraindicated; for Class C (severe): contraindicated. Verapamil is extensively metabolized in liver; dose reduction recommended in significant hepatic impairment. Tarka is contraindicated in severe hepatic impairment. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. No approved pediatric dosing. |
| Geriatric use | Initiate at lower end of dosing range (e.g., 1 mg/180 mg once daily) due to possible decreased renal function and increased sensitivity to hypotension. Monitor renal function and electrolytes closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TARKA (TARKA).
| Breastfeeding | Verapamil is excreted in human milk with an M/P ratio of approximately 0.6; trandolaprilat excretion is unknown. Due to the potential for hypotension and renal effects in nursing infants, TARKA is not recommended during breastfeeding. |
| Teratogenic Risk | TARKA (trandolapril/verapamil) is contraindicated in pregnancy. ACE inhibitors, including trandolapril, are associated with fetal renal dysfunction, oligohydramnios, skull ossification defects, and fetal death. Risk is highest in the second and third trimesters. Verapamil may cause fetal bradycardia, but data are limited. Use is not recommended at any trimester due to potential harm. |
■ FDA Black Box Warning
Use in pregnancy: Drugs acting directly on the renin-angiotensin system can cause fetal injury and death. Discontinue as soon as possible when pregnancy is detected.
| Serious Effects |
["Hypersensitivity to trandolapril, verapamil, or any component","History of angioedema with prior ACE inhibitor therapy","Severe hypotension or cardiogenic shock","Sick sinus syndrome or advanced heart block (except with pacemaker)","Atrial fibrillation/flutter with accessory bypass tract (e.g., Wolff-Parkinson-White)","Concurrent use with dofetilide or other drugs causing QT prolongation"]
| Precautions | ["Angioedema: Risk with ACE inhibitors, especially in patients with history.","Hypotension: May occur, especially in volume-depleted patients.","Renal impairment: Monitor renal function; risk of acute renal failure.","Hyperkalemia: ACE inhibitors increase potassium; caution with potassium-sparing diuretics.","Heart block/bradycardia: Verapamil may worsen AV nodal conduction; avoid in advanced heart block.","Hepatic impairment: Reduce dose in severe liver disease."] |
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| Fetal Monitoring | Monitor maternal blood pressure, renal function, and serum potassium during therapy. If inadvertent exposure occurs during pregnancy, perform fetal ultrasound to assess amniotic fluid volume and renal function. Monitor for fetal bradycardia with verapamil exposure. |
| Fertility Effects | ACE inhibitors may affect maternal renal function and potentially impact fertility through hemodynamic changes. Verapamil has been associated with reversible reductions in sperm motility and function in some animal studies; human data are limited. |