The results of 7 open-label clinical studies on oxcarbazepine (OXC) in different neuropathic pain conditions, sharing the same protocols, were pooled together in order to evaluate whether the results obtained in the individual trials were confirmed in the pooled analysis of this larger sample, providing more evidence for efficacy and tolerability of OXC in these conditions. Eligible patients (>18 years old) with a diagnosis of neuropathic pain were enrolled in seven open-label trials, consisting of a one-week prospective Screening Phase followed by an eight-week Treatment Phase. Treatment with OXC was initiated at 150 mg/day, and the daily dose was increased by 150 mg/day on a 2-3 day basis to the maximum tolerated dose over four weeks, up to 1800 mg/day. The primary outcome measure was the change in the actual pain rating assessed on the visual analogue scale (VAS) between the end of the Screening Phase and the end of the Treatment Phase. One hundred and thirty-six patients were enrolled in the trials. The mean VAS score dropped from 77.13 at the end of the Screening Phase to 38.41 at the end of the trial for a mean reduction of 50.2%. The percentage of responders (mean VAS score reduction > or = 50%) was 49.2%. OXC was well tolerated, with the most common adverse events consisting of vertigo, tremor, somnolence, hypotension and nausea. The results of this analysis suggest that OXC administered as monotherapy is an efficacious and safe option for the symptomatic treatment of pain associated with neuropathies.
To investigate the antianginal efficacy and tolerability of felodipine, a new dihydropyridine calcium antagonist, 20 patients with stable exertional angina, not completely controlled by beta-blocker monotherapy, entered a randomized, double-blind, placebo-controlled, crossover study. Patients on standard beta-blocker therapy, who had at least 3 weekly anginal episodes and a reproducible exercise test (stopped for angina and ECG signs of ischaemia) at the end of 2 weeks placebo treatment, were eligible for the study. They were randomized to one sequence of treatment: felodipine 5 mg twice daily for 2 weeks followed by placebo for a further 2 weeks, or vice versa. Beta-blocker treatment was unchanged throughout the study. A treadmill test was carried out at the end of each crossover period, 2-4 h after drug administration. The number of anginal attacks and nitroglycerin consumption was recorded on a diary card. At rest, felodipine significantly (P less than 0.05) reduced standing systolic but not diastolic blood pressure. Heart rate was not modified by the active treatment. At ischaemic threshold and at peak exercise, heart rate, systolic blood pressure and rate-pressure product remained unchanged. Exercise duration was increased by felodipine (P less than 0.01) and maximal ST change was reduced (P less than 0.01). Time to 1 mm ST depression was prolonged non-significantly by felodipine (basal 5.7 +/- 1.5, felodipine 7.4 +/- 2.0, placebo 6.6 +/- 1.5 min). The number of patients who stopped exercise due to angina and ST change was 20/20 at baseline, 16/20 with placebo and 10/20 with felodipine. Felodipine significantly reduced weekly anginal episodes (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
1 Felodipine is a new calcium-antagonist dihydropyridine derivative with a high degree of selectivity for smooth muscle of arteriolar resistance vessels, as opposed to cardiac cells. 2 In this double-blind, cross-over study the antihypertensive efficacy and tolerability of the new extended release (ER) formulation of felodipine 10 mg, once daily, in patients with mild essential hypertension was evaluated. After a 4-week single-blind placebo period 28 patients (15 males; mean age 48 ± 12 years) were randomized to receive felodipine 10 mg ER once daily or placebo for 4 weeks and the alternative treatment for a further 4 weeks. Supine blood pressure and heart rate were measured in the out-patients department every 2 weeks, 22-24 h after the last drug administration. 3 Felodipine 10 mg ER induced a significant reduction in blood pressure in comparison with placebo (from 149 ± 16/97 ± 6 to 140 ± 12/89 ± 6 mm Hg). Heart rate remained unchanged. Seven patients dropped-out; five during felodipine ER administration and two during placebo.4 A once daily dose of felodipine ER significantly reduces blood pressure in mild hypertensive patients 22-24 h after administration. It is well tolerated and the adverse events are related to its pharmacodynamic effects.
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