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) |
| Molecular Weight | Trandolapril: 430.54 Da; Verapamil: 454.6 Da |
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 | Avoid use in first trimester due to risk of teratogenicity (renal dysfunction, oligohydramnios, fetal skull defects). |
| 2nd trimester | Contraindicated in second trimester due to fetal toxicity (oligohydramnios, IUGR, fetal hypotension). |
| 3rd trimester | Contraindicated in third trimester due to fetal and neonatal toxicity (renal failure, hyperkalemia, hypotension). |
Clinical note
Comprehensive clinical and safety monograph for TARKA (TARKA).
| Placental transfer | Both components cross the placenta; trandolaprilat (active metabolite) shows significant transfer in animal studies. |
| Breastfeeding | Verapamil is excreted in breast milk in low concentrations; trandolapril is excreted in minimal amounts. Monitor infant for hypotension and renal effects. Consider alternative antihypertensives if breastfeeding. |
■ 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 verapamil, trandolapril, or any ACE inhibitorHistory of angioedema from prior ACE inhibitor therapyPregnancy (second and third trimesters)Severe hypotensionCardiogenic shockSick sinus syndrome or 2nd/3rd degree AV block (unless pacemaker is in place)Atrial fibrillation/flutter with accessory bypass tract (e.g., Wolff-Parkinson-White syndrome)Severe left ventricular dysfunction (ejection fraction <30%)
| 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. |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L4 (Possibly Hazardous) |
| 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. |
| 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. |
| Avoid grapefruit and grapefruit juice. Limit alcohol intake as it can increase hypotensive effects. Avoid excessive potassium intake from potassium-rich foods or salt substitutes. Take with food to reduce GI upset. |
| Clinical Pearls | Tarka (trandolapril/verapamil) combines an ACE inhibitor with a non-dihydropyridine calcium channel blocker. Monitor renal function and serum potassium, especially in patients with renal impairment or on potassium-sparing diuretics. Avoid in patients with left ventricular dysfunction, heart block, or sick sinus syndrome. Titrate slowly due to risk of bradycardia and hypotension. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly without consulting doctor. · Notify doctor if experiencing symptoms like fainting, slow heartbeat, swelling of face/lips/tongue, or difficulty breathing. · Avoid salt substitutes containing potassium unless approved by doctor. · May cause dizziness – avoid driving until you know how it affects you. · Report any signs of infection, such as fever or sore throat, as ACE inhibitors can lower white blood cell count. · Do not use during pregnancy; discuss effective contraception if of childbearing potential. |