Acetazolamide for Monge's disease: efficiency and tolerance of 6-month treatment.
BACKGROUND
Monge's disease is characterized by an excessive erythrocytosis, frequently associated with pulmonary hypertension, in high-altitude dwellers. It has a considerable impact on public health in high-altitude regions. A preliminary study demonstrated the efficiency of acetazolamide (Acz) (250 mg/d for 3 wk) in reducing serum erythropoietin and hematocrit.


OBJECTIVE
Evaluate the efficacy and tolerance of a 6-month treatment with 250 mg Acz that could be chronically implemented and its effects on pulmonary artery pressure and cardiac function.


METHODS
A two-phase study was performed in patients (hematocrit > or = 63%) from Cerro de Pasco, Peru (4,300 m). First phase: a double-blind, placebo-controlled study in 55 patients who received a single dose of either 250 mg Acz (n = 40) or placebo (n = 15) by daily oral administration for 12 weeks. Second phase (open label): after a 4-week washout period, all patients received 250 mg Acz for 12 weeks. Hematocrit, blood gases, clinical outcome, and pulmonary artery circulation were evaluated.


RESULTS
First phase: Acz decreased by 44% the number of polycythemic subjects (P = 0.02), decreased hematocrit from 69 to 64% (P < 0.001), and increased arterial O(2) pressure from 42 to 45 mm Hg (P < 0.001). No severe adverse effect or hypokalemia was recorded. The second phase reproduced the effects observed during the first phase, without cumulative effects on hematocrit. A 4-week washout restored basal hematocrit. Only patients who received Acz for 6 months showed a clear reduction in pulmonary vascular resistance.


CONCLUSIONS
Acz reduces erythrocytosis and improves pulmonary circulation in Monge's disease without adverse effects. Its implementation as a chronic treatment for this disease appears efficient and safe.
Richalet
Jean-Paul
JP
Université Paris 13, Laboratoire Réponses cellulaires et fonctionnelles à l'hypoxie, EA 2363, ARPE, UFR SMBH, Bobigny, France. richalet@smbh.univ-paris13.fr
Rivera-Ch
Maria
M
Maignan
Maxime
M
Privat
Catherine
C
Pham
Isabelle
I
Macarlupu
Jose-Luis
JL
Petitjean
Olivier
O
León-Velarde
Fabiola
F
D000086:Acetazolamide / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000532:Altitude Sickness / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000704:Analysis of Variance; D002257:Carbonic Anhydrase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002302:Cardiac Output / Q000187:drug effects; D002908:Chronic Disease; D004311:Double-Blind Method; D004452:Echocardiography; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy; D000860:Hypoxia / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010568:Peru; D011086:Polycythemia / Q000188:drug therapy*; D011446:Prospective Studies; D014262:Tricuspid Valve Insufficiency / Q000209:etiology
D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide