Trandolapril dosing

Trandolapril 1 mg initially target dose 4 mg once daily. 

Initial dose The recommended initial dosage of trandolapril for patients not receiving a diuretic is 1 mg/day (2 mg in black patients). Adjust dosage according to the BP response. Make dosage adjustments at intervals of 1 week or more. Most patients have required dosages of 2 to 4 mg/day. 

Maintenance - Patients inadequately treated with once daily dosing at 4 mg may be treated with twice-daily dosing. If BP is not adequately controlled with trandolapril monotherapy, a diuretic may be added. 

Concomitant diuretic - In patients being treated with a diuretic, symptomatic hypotension can occasionally occur following the initial dose of trandolapril. To reduce the likelihood of hypotension, if possible, discontinue the diuretic 2 to 3 days prior to beginning therapy with trandolapril. If BP is not controlled with trandolapril alone, resume diuretic therapy. If the diuretic cannot be discontinued, give an initial dose of 0.5 mg trandolapril with careful medical supervision for several hours until BP has stabilized. Titrate dosage as described above to the optimal response. 

If we are quite certain that ACE immobilized at the surface of the endotheliaf celfs is physiologicaliy more important than is the circulating enzyme (197), we do not know yet what is the relative importance of its bland C-terminal active sites. We do not know how they possibly affect the activity of each other. We do not know the physiological role of the N-acetyl SDKP, a relatively specific substrate of the N-terminal active site. We may still discover other natural substrates for endothelial and epithelial ACE. We do not fully understand the basis of differences in the various daily doses of ACE inhibitors as usually prescribed, from trandolapril 2 mg/day to lisinopril 80 mg/day, and the consequences of dose choices. 

Gokel Y, Paydas S, Duru M. High-dose verapamU-trandolapril induced rhabdomyolysis and acute renal failure. Am J Emerg Med 2000 18(6) 738-9. 

No long-term endpoint studies in patients with diabetic nephropathy have yet been published, but in nondiabetic nephropathy data from two studies are now available. In the COOPERATE trial 263 Japanese patients with nondiabetic renal disease (calculated GFR 20-70 mL/min) were randomly assigned ARB (losartan, 100 mg daily), ACE-1 (trandolapril, 3 mg daily) or a combination of both drugs at equivalent doses. After 3 years, significantly fewer patients [10 (11%) of 85] in the dual-blockade group had reached the combined primary endpoint of time to doubling of serum creatinine or ESRD... 

Other single-dose studies have shown that food had no statistically significant effect on the pharmacokinetics of lisinopril, or enalapril, and its active metabolite, enalaprilat. Similarly, food had minimal effects on the pharmacokinetics of cilazapril (AUC decreased by only 14%). Food caused small, but statistically significant increases in the time to reach maximum plasma levels of quinapril and its active metabolite. However, as the increase was less than 30 minutes this is not expected to alter the therapeutic effect. Likewise, the manufacturers of spirapril briefly mention in a review that food delayed its absorption by 1 hour, it did not affect the bioavailability of spirapril or spiraprilat, its active metabolite. Other manufacturers state that food had no effect on the absorption of fosinopril 11,12 ramipril, or trandolapril. ... 

Other ACE inhibitors. A placebo-controlled, randomised, crossover study in 16 hypertensive patients found that indometacin 50 mg twice daily reduced the blood pressure-lowering effects of cilazapril 2.5 mg daily. The reduction was greater when cilazapril was added to indometacin than when indometacin was added to cilazapril (approximately 60% versus 30% reduction in hypotensive effect measured 3 hours after the morning dose). The antihypertensive effects of perindopril 4 to 8 mg daily were also found to be reduced by about 30% by indometacin 50 mg twice daily in 10 hypertensive patients. A brief mention is made in a review that the pharmacodynamics of ramipril were unaffected by indometacin (dosage not stated) given to healthy subjects for 3 days. Indometacin 25 mg three times daily did not alter the hypotensive effects of trandolapril 2 mg daily in 17 hypertensive patients. ... 

In a study in 19 healthy subjects, trandolapril 2 mg daily for 13 days did not atFect the pharmacodynamics of a single 25-mg dose of warfarin given on day 8. 

Meyer BH, Muller FO, B enhorst PN, Luus HG, De La Rey N. Multiple doses of trandolapril do not affect warfarin pharmacodynamics. SAfrMedJ (1995) 85, 768-70. 

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