Long-term Effect of Almitrine Bismesylate in Patients with Hypoxemic Chronic Obstructive Pulmonary Disease

Abstract

A long-term evaluation of the therapeutic efficacy and safety of oral almitrine bismesylate (AB) (50 mg twice daily) was made on 25 patients with COPD and moderate hypoxemia residing at an altitude of 1,500 m in a double-blind placebo-controlled study. Thirteen patients receiving AB (baseline PaO2, 54.3 +/- 4.9 mm Hg; mean +/- SD) and 12 patients receiving placebo (baseline PaO2, 53.0 +/- 4.1 mmHg) were periodically followed by arterial blood gas and other pulmonary function studies and plasma levels of AB. Eight patients receiving AB and nine patients receiving placebo were followed for 1 yr; all patients were followed for at least 90 days. AB administration resulted in an increase in PaO2 to 62.2 +/- 9.3 mm Hg (p less than 0.01) on Day 28. The increase was maintained until Day 360 (63.8 +/- 4.6 mm Hg; p less than 0.01). The mean plasma concentration of AB on Day 28 was approximately one-half that on Day 90 when the plasma level reached a near maximum. AB was associated with weight loss (five of 13 patients receiving AB lost more than 10% of their baseline body weight) and peripheral paresthesias of the lower extremities (three patients), both occurring at the peak plasma levels of the drug. We conclude that AB causes a long-term improvement in arterial oxygenation in hypoxemic patients with COPD residing at an altitude of 1,500 m. Our data suggest that lower doses of AB might produce the same effect on PaO2 with less adverse associated effects, and this should be tested in future studies.

Primary alveolar hypoventilation and response to the respiratory stimulant almitrine

“…Transaminases may rise. A loss of body weight of 10% has been reported in 40% of cases, 6 as was seen in this case. It seems unlikely that the fall in weight was responsible for improved gas exchange because the weight loss was not seen during the first period on almitrine, when blood gases also normalized.…”

“…A well‐reported side‐effect of almitrine therapy is peripheral neuropathy. This may occur in 14% of cases and is dose dependent and slowly reversible off the drug 6 . Transaminases may rise.…”

Evolution of Physiological Variables in Patients with Chronic Obstructive Pulmonary Disease before and during Long-Term Oxygen Therapy

“…The therapeutic re gimen did not change after the onset of LTO and it in cluded, in most of the patients, oral theophylline, aerosols of p2-agonists and physiotherapy. No patients received almitrine which could have improved ABG [15,16], The most important difference between the two periods is that patients were closely followed-up after initiation of LTO, with regular monitoring at the outpatient clinic, at least once every trimester, and in some patients once every 2 months, which was differ ent from the period T(,-T| (1 or 2 visits/year). Further more, as soon as LTO was started, patients were regu larly visited at home by a technician of our depart ment who checked the 0 2 delivery system and particularly the concentrators.…”

Pharmacological Treatment of Hypoxemia during One-lung Ventilation

“…6 Peripheral neuropathy related to almitrine has been observed in patients who received this drug for several months, usually with complete recovery, 8 and is related to high plasma concentrations of almitrine (400 ng/ml). 9 However, when low-dose almitrine is administered for a short time its plasma concentration is less than the concentration seen with long-term therapy 6,7 and returns to values close to zero within 12 h after cessation of the infusion. 7 Almitrine and inhaled nitric should not be used routinely.…”