RandD Isradipine: and nifedipine have similar antianginal efficacy ...

A randomised double-blind study was conducted to compare the efficacy of isradipine [PN 200-110; Sandoz], a new dihydropyridine calcium antagonist, and nifedipine in the treatment of patients with stable angina pectoris. After a 2-week washout period, 11 patients received isradipine 2.S, Sand 7.Smg tid for 2 weeks at each dose level or nifedipine S, 10 and 20mg tid for 2 weeks at each dose level. Patients were then crossed over to alternate treatment for a further 6 weeks. Symptom-limited treadmill exercise tests "",ere performed at' each assessment.

After 6 weeks, the number of anginal attacks decreased from 16.9 at baseline to 1S.3 with nifedipine and to 14.9 with isradipine. Anginal severity scores decreased from 1.8 to 1.3 and 1.S, respectively. The number of nitroglycerin [glyceryl trinitrate] tablets taken reduced from 28.6 to 8.8 among nifedipine recipients and to 6.9 among isradipine recipients. There were no significant differences between the 2 treatment groups in these parameters. Systolic BP during exercise increased after 4 weeks from 162.7mm Hg at baseline to 171.4mm Hg with nifedipine compared with 1S6.4mm Hg with isradipine. Time to onset of angina increased from 426.4 seconds at baseline to 641 seconds after 4 weeks and 66S.6 seconds after 6 weeks in the nifedipine-treated group compared with 708.S and 688 seconds, respectively, in the isradipine-treated group. At 6 weeks, time to exercise termination increased significantly from 62S.3 to 943.6 seconds with nifedipine and 912.3 seconds with isradipine. Adverse effects included depression (1 patient receiving isradipine vs 1 receiving nifedipine), headache (1 vs 4), gastrointestinal problems (1 each), shortness of breath (1 vs 0) and nervousness (1 vs 0).

The authors concluded that there were no significant differences in either clinical or exercise test variables between isradipine and nifedipine in the treatment of patients with stable angina pectoris. Handler CE, Rosenthal E, Tsagadopoulos D, Najm Y. International Journal of Cardiology 18: 15-26, Jan 1988 1642

. . . and isradipine and hydrochlorothiazide monotherapy have comparable efficacy in mild to moderate hypertension ...

In order to assess the efficacy of isradipine as a possible first step antihypertensive agent , 98 patients with mild to moderate hypertension (sitting diastolic BP of 9S-120mm Hg) were randomised to receive isradipine S-10mg (n = 48) or hydrochlorothiazide 2S-S0mg bid (SO) for 10 weeks following a 3-week washout period, in a multicentre double-blind trial.

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Sitting BP decreased by 18/17mm Hg among isradipine recipients and by 20/14mm Hg among hydrochlorothiazide recipients, (p < 0.001 vs baseline; p < O.OS between groups for diastolic BP only). Sitting diastolic BP was ~ 8Smm Hg in 72% of isradipine recipients and 46% of hydrochlorothiazide recipients and sitting diastolic BP was ~ 90mm Hg in 89 and 86% of patients, respectively.

The most frequently reported adverse effects were headache (8 isradipine recipients vs 8 hydrochlorothiazide recipients), dizziness (S vs S), chest pain (1 vs 3), palpitations (4 vs 2), oedema (9 vs 1; P < 0.01), abdominal discomfort (6 vs 2), weakness (2 vs 4) and fatigue (S vs 3).

Thus, isradipine '. _ . in doses 5 to 10 mg twice daily is safe and as effective as HCTZ [hydrochlorothiazide1 as a monotherapy of mild to moderate hypertension'. Mohanty PK , Gonasun LM, Goodman RP, Kirkendal WM, Kontos HA. et al. American Journal of Hypertension 1: 241S·244S, Jul1988 ""

... but isradipine has less effect than verapamil on the steady-state kinetics of digoxin

Patients receiving digoxin are frequently coadministered calcium channel blockers as adjuncts in several therapeutic settings. A trial was therefore conducted to compare the effects 01 isradipine with those of verapamil on the steady-state kinetics of orally administered digoxin . 19 healthy male volunteers received digoxin 0.2Smg bid for 2 consecutive 2-week periods. Volunteers were randomised to receive either isradipine 2 .Sm~ bid for 2 days, Smg bid for 2 days then Smg tid for 10 days or verapamil 80mg bid for 4 days then 80mg tid for 10 days, with digoxin alone taken for the other 2-week period.

Mean 0-12 hour urinary digoxin elimination increased from 106.8.ug after 2 weeks of · digoxin therapy to 164.S.ug after 2 weeks of digoxin + verapamil administration and from 107.S to 123.9.ug after isradipine administration. Mean 12-24 hour elimination increases were 11S.6 to 134.3.ug and 113.9 to 123.2.ug for verapamil and isradipine, respectively. Significant increases in AUC (p < 0.001), mean steady-state serum digoxin concentration (p < 0.001) and peak serum digoxin concentration (p < 0.001) were evident in volunteers after 2 weeks of verapamil therapy . Volunteers who received isradipine for 2 weeks were found to have an increase in peak serum digoxin concentration (p < 0.05) only. No clinically significant adverse effects were noted.

The authors concluded that ' ... it is highly unlikely that the interaction of isradlplne with digoxin Is of clinical importance. It appears that, in contrast to verapamil, no special precautions are indicated when Isradipine is prescribed together with digoxin.'

Rodin SM, Johnson SF, Wilson J, Ritchie P, Johnson J. Clinical Pharmacology and Therapeutics 43: 668·672, Jun 1988 7640

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