[e-farmacos] Consulta sobre diosmectita (cont.)

["Canas, Martin" <macanas@netverk.com.ar>]

Estimada Ninoska,

La disomectita es un principio activo que se ha utilizado para el tratamiento de la diarrea y otros trastornos gastrointestinales. 

En muchos paises (Francia, Italia, Rumania, Colombia) se comercializa con el 
nombre SMECTA (ver informacion comercial en frances) 
http://www.doctissimo.fr/medicament-SMECTA.htm

La  busqueda en Sietes (http://www,sietes.org) nos remite a la cita: Miselli M, Zanfi D. Diosmectite. Informazioni sui Farmaci 1997;21:95-7.

La busqueda en Pubmed con los filtros metodologicos para ensayos clinicos controlados arrojo los siguientes resultados:
1: Rom J Intern Med. 2004;42(1):191-7. The effect of two antidiarrhoeal drugs on the psychosocial adjustment to illness in chronic functional diarrhoea.
Dumitrascu DL, Stanculete M, Mitrea I, Dumitrascu DM, Farcas A.
3rd Medical Department, Iuliu Hatieganu University of Medicine & Pharmacy, 
Cluj Napoca, Romania. ddumitrascu@cluj.astral.ro
BACKGROUND: Chronic functional diarrhea is an embarrassing symptom, causing 
the impairment of the quality of life. AIM: We looked for the effect of two
antidiarrheal drugs, diosmectite and loperamide on the psychosocial 
adjustment to illness, a predictor for the health-related quality of life, in chronic functional diarrhea. METHODS: Prospective controlled randomized trial including 50 consecutive patients with chronic functional diarrhea. They received either diosmectite 3 g b.i.d (n=25, 11M/14F, age 43+/-12 years) or loperamide 2 mg b.i.d. (n=25, 12M/13F, 47+/-11 years) for 2 weeks. Diarrhea and four other digestive symptoms were evaluated on a 0-16 scale, as well as patient's satisfaction (scale 1-10) and physician's satisfaction (scale 0-4).  
Psychosocial adjustment to illness was assessed with the PAIS-SR scale. RESULTS: Symptom score for diarrhea was reduced from 10.5+/-5.7 to 2.6+/-1.2 (mean+/-SD),  p<0.001 by diosmectite and from 8.5+/-4.2 to 1.2+/-0.6, p<0.0001 by loperamide. Diosmectite had a stronger effect than loperamide on accompanying pain (p<0.05) and bloating (p<0.01), but not on nausea, anorexia and emesis. The overall ratings of the patient's satisfaction (8.7+/-0.9 vs. 8.2+/-1.1, NS) and physician's satisfaction (3.2+/-0.3 vs. 3.1+/-0.4, NS) were similar.

Psychological adjustment to illness was not changed for following items:  health care orientation and domestic environment. Diosmectite improved more than loperamide the psychological distress (from 12.7+/-3.8 to 7.7+/-2.1 vs. 11.8+/-3.3 to 9.05+/-2.2, p<0.05), vocational environment (from 3.2+/-1.1 to 2.2+/-1.2 vs. 3.3+/-1.2 to 3.4+/-1.5, p<0.05) and sexual relationship scores (from 6.4+/-2.2 to 3.0+/-1.5 vs. 7.2+/-2.2 to 5.5+/-2.1, p<0.05). Both drugs similarly improved the items: family relationship and social environment. CONCLUSIONS: Diosmectite and loperamide are both potent drugs for chronic functional diarrhea. Diosmectite has better effects on associated symptoms  and some items of psychosocial adjustment to illness (distress, sexual activity  and vocational environment). 
2: J Pediatr Gastroenterol Nutr. 2001 Jan;32(1):71-5. 
Smectite in the treatment of acute diarrhea: a nationwide randomized  controlled study of the Italian Society of Pediatric Gastroenterology and Hepatology (SIGEP) in collaboration with primary care pediatricians. SIGEP Study Group  for Smectite in Acute Diarrhea. Guarino A, Bisceglia M, Castellucci G, Iacono G, Casali LG, Bruzzese E,  Musetta A, Greco L; Italian Society of Pediatric Gastroenterology and Hepatology  Study Group for Smectite in Acute Diarrhea. Department of Pediatrics, University Federico II, Naples, Italy. alfguari@unina.it 
BACKGROUND: Childhood gastroenteritis is associated with considerable health costs. The natural clay dioctahedral smectite increases intestinal barrier function and is effective against infectious diarrhea in children in  developing countries. The purpose of this work was to investigate the efficacy of  smectite in Italian children with acute diarrhea of mild to moderate severity.  METHODS: A national, prospective, randomized, case-controlled study was performed in collaboration with primary care pediatricians. Children seen by  pediatricians for acute gastroenteritis were treated with oral rehydration solution (ORS) alone or ORS with smectite. Parents returned a form in which total duration  of diarrhea, incidence of vomiting and fever, persistence of diarrhea for more  than 7 days and hospital admissions were recorded. RESULTS: Eight hundred four children with acute diarrhea were randomly assigned to treated or control groups. Administration of smectite was associated with significant reduction  of the duration of diarrhea, as judged by stool frequency and consistency. The incidence and duration of vomiting and fever were not different. Diarrhea  lasted more than 7 days in 10% of treated and in 18% of control children (P <  0.01). Hospital admission was necessary in seven treated and six control children.  No side effects were observed. CONCLUSIONS: Smectite reduces the duration of diarrhea and prevents a prolonged course. It may therefore consistently  reduce the costs of gastroenteritis. 
3: Strahlenther Onkol. 2000 Apr;176(4):173-9. 
[Prevention of radiation-induced diarrhea by smectite. Results of a  double-blind randomized, placebo-controlled multicenter study] 
[Article in German] 
Hombrink J, Frohlich D, Glatzel M, Krauss A, Thiel HJ, Meier J, Hamann D,  Mucke R, Glaser FH, Kost S. 
Abteilung fur Strahlentherapie, Zentralklinikum Augsburg. 
PURPOSE: Diarrhea and abdominal pain are well-known side effects abdominal  or pelvic of radiation therapy that may lead to interruption of treatment in serious cases. In recent trials the silicate smectite has proven a promising drug in the prophylaxis of these adverse events. The presented trial aimed  at the verification of earlier studies and the evaluation of a dose-effect relationship. PATIENTS AND METHODS: Between April 1994 and May 1995, a total  of 176 patients obtaining radiotherapy of the pelvis or the abdomen were  evaluated in a double-blind, randomized placebo-controlled investigation regarding the prophylactic effect of smectite (= Colina) against radiotherapy-induced diarrhea. During the whole period of radiotherapy 85 patients obtained 2 x 6  g smectite daily and 91 patients received 2 x 6 g placebo. The primary end  point of the analysis was the time to the first appearance of diarrhea (> or = 3  pappy stools). RESULTS: All 176 patients were evaluated according to an intent-to-treat analysis. There was no significant difference between the prophylactic effects of smectite and placebo. For an explorative post-hoc analysis the total study group was split up into 2 subgroups, one with an irradiated small bowel volume < or = 837.5 ml, the other with a small bowel volume > 837.5 ml (median); the analysis indicated that the first subgroup showed a benefit for the smectite-treated patients in contrast to the  placebo treatment (32 vs. 18 calendar days to the first appearance of diarrhea).  This benefit was statistically not significant. CONCLUSION: Prophylactic  application of smectite during irradiation of the pelvis and the abdomen can delay the development of radiotherapy-induced diarrhea, a statistical significance  could not be verified neither in the total study group nor in the post-hoc  subgroup analysis. 
4: Fortschr Med. 1994 Aug 30;112(24):6p. 
[Placebo-controlled, double-blind clinical trial of smectite in acute  pediatric diarrhea][Article in German] [No authors listed] 
Medizinischen Fakultat der Universitat Alexandria und dem Militrkrankenhaus Mostafa Kamel, Alexandria, Agypten. 
5: J Pediatr Gastroenterol Nutr. 1994 Aug;19(2):251-4. Comment in:     J Pediatr Gastroenterol Nutr. 1996 Jan;22(1):112-4. Earth, wind, and fiber: is there a drug to treat acute diarrhea? Rhoads JM. 
6: Southeast Asian J Trop Med Public Health. 1994 Mar;25(1):157-62. Control randomized study of rehydration/rehydration with dioctahedral  smectite in ambulatory Thai infants with acute diarrhea.Lexomboon U, Harikul S,  Lortholary O. 
Pediatric Gastroenterology Unit, Children's Hospital, Bangkok, Thailand. 
The study was performed to assess the efficiency, acceptability and safety  of dioctahedral smectite (DS) associated with rehydration in ambulatory infants with acute diarrhea. Sixty-six Thai infants, aged 1-24 months were randomly divided into 2 groups. One group of 32 infants (control group) received oral  or intravenous rehydration, the other group of 34 infants (DS group) received  the rehydration with DS. Both groups were comparable for sex, age, weight, diet, duration of diarrhea, body temperature, nutritional and dehydration status. Bacteriological stool examination was positive in 22% in control group and  26% in DS group for Salmonella, Shigella, Campylobacter, enterotoxigenic  Escherichia coli and Plesiomonas sp. Rotavirus was found in 25% of the control group and  29% of the DS group. Seventy-two hours after therapy, 34% of infants were cured  in the control group compared to 71% in DS group (p < 0.01) and 5 days after  the beginning of treatment, 34% still had diarrhea in the control group compared  to 12% in DS group (p = 0.04). The acceptability of DS was considered to be  good in 30 infants (88%). No major side effect was observed. In conclusion, DS with rehydration shortens the course of acute diarrhea in ambulatory infants and  may reduce the occurrence of prolonged diarrhea. DS is well tolerated in infants with acute diarrhea. 
7: J Pediatr Gastroenterol Nutr. 1993 Aug;17(2):176-81. Comment in:     J Pediatr Gastroenterol Nutr. 1994 May;18(4):505-6. 
Smectite in acute diarrhea in children: a double-blind placebo-controlled clinical trial. 
Madkour AA, Madina EM, el-Azzouni OE, Amer MA, el-Walili TM, Abbass T. 
Alexandria University, Faculty of Medicine, Egypt. 
Dioctahedral smectite (DS) a natural adsorbent clay capable of adsorbing viruses, bacteria, and other intestinal irritants in vitro, is claimed to possess beneficial "antidiarrheal" properties. This study tested the effect  of DS on the duration of diarrhea and the frequency and amount of liquid  stools. Ninety well-nourished boys, aged 3-24 months, with acute watery diarrhea and mild, moderate, or severe dehydration were included in a randomized double-blind, placebo-controlled trial. After initial rehydration, they  received DS or placebo (1.5 g freshly dissolved in 50 ml of water, four times daily  for 3 days) along with oral rehydration solution (ORS) and adequate feeding. The clinical characteristics of both groups were comparable on admission.  Patients in the smectite group had a significantly shorter duration of diarrhea (mean  +/- SD, 54 +/- 16 vs. 73 +/- 13 h) and significantly fewer stools (2.6 +/- 0.8  vs. 3 +/- 0.7 on second day; 1.9 +/- 0.7 vs. 2.4 +/- 0.7 on third day; and 11.3  +/- 3.2 vs. 13.8 +/- 3 overall). The amount of liquid stools was not  significantly reduced. Weight gain at 24, 48, and 72 h and on recovery was significantly higher in the smectite group despite the comparable fluid and food intake in both groups. These results suggest a beneficial effect of DS in shortening  the duration of diarrhea and reducing the frequency of liquid stools in children rehydrated with ORS. 
8: Southeast Asian J Trop Med Public Health. 1992 Sep;23(3):414-9. 
Control study of oral rehydration solution (ORS)/ORS + dioctahedral smectite  in hospitalized Thai infants with acute secretory diarrhea. 
Vivatvakin B, Jongpipatvanich S, Harikul S, Eksaengri P, Lortholary O. 
Department of Pediatrics, Chulalongkorn University Hospital, Bangkok,  Thailand. 
Dioctahedral smectite, a non systemic antidiarrheal agent, is mucoprotective  and absorbs enterotoxins and rotavirus as demonstrated in animal models.  Smectite has been successfully used in various countries in children and adults with acute diarrhea. This study was to assess the efficiency of smectite  associated with rehydration in infants with acute secretory diarrhea. Sixty-two hospitalized Thai infants, aged 1-24 months, with acute secretory diarrhea  were randomly divided into 2 groups receiving (1) oral rehydration solution (ORS)  (30 cases), (2) ORS and Smectite (3.6 g/day) (32 cases). Both groups were  comparable for age, weight, nutritional status and duration of symptoms before  treatment. All 62 infants received lactose free formula and chicken rice soup as the standard diet. Stool frequency, weight change and duration of diarrhea were recorded. The mean duration of diarrhea was 84.7 +/- 48.5 hours in group 1,  and 43.3 +/- 25.1 hours in group 2 (p = 0.005). The number of infants with  diarrhea was significantly lower in group 2 on Day 1 (p < 0.01) and Day 3 (p =  0.001); furthermore 27% of infants in group 1 and 3% in group 2 had still diarrhea  on Day 5. The stool frequency and weight changes were not statistically  different in the two groups. No major side effects were observed except two cases of vomiting and hardened stools. It is concluded that (1) Smectite shortens the course of acute secretory diarrhea in Thai infants; (2) smectite may reduce  the occurrence of prolonged diarrhea; furthermore (3) in our study dioctahedral smectite was found to be safe in children aged 1 to 24 months. 
 9: J Pediatr Gastroenterol Nutr. 1992 May;14(4):413-9. Effect of diosmectite on intestinal permeability changes in acute diarrhea:  a double-blind placebo-controlled trial. Dupont C, Moreno JL, Barau E, Bargaoui K, Thiane E, Plique O. 
 The effect of diosmectite on intestinal permeability changes in acute  diarrhea was measured during a double-blind placebo-controlled trial carried out in  59 Gabonese children aged 5-35 months. Intestinal permeability tests (IPTs), measuring the urinary elimination of orally administered lactulose and  mannitol at a dosage of 1 g/10 kg each, were performed during the morning following admission and repeated 2 days later after treatment by diosmectite or  placebo. During the first IPT, urine volume and lactulose and mannitol urinary  recoveries were comparable in the diosmectite and in the placebo groups: 50 vs. 35.5 ml (median; p = 0.21), 1.01 vs. 1.27% (p = 0.35), and 2.20 vs. 2.87% (p =  0.12). As a result, the lactulose/mannitol (L/M) ratio was similar in the two groups: 44.44 vs. 35.33% (p = 0.98). During the second IPT, the urinary lactulose recovery decreased similarly in both groups (-0.18 vs. -0.29%; p = 0.76), whereas the urinary mannitol recovery exhibited opposite variations, the increase in the diosmectite group (+ 1.43%) contrasting significantly with  the decrease in the placebo group (-0.47%; p = 0.01). When comparing the first  and the second IPT, the decrease of the L/M ratio was significant in the  diosmectite group (44.44 vs. 28.32%; p = 0.02) and not in the placebo group (35.33 vs. 48.23%; p = 0.91). During gastroenteritis, diosmectite appears to enhance absorption of mannitol, a marker of intestinal absorptive area. 10: Ann Pediatr (Paris). 1991 Nov;38(9):633-6. 
[The efficacy of smectite in acute infantile diarrhea, compared to a placebo  and loperamide] [Article in French] 
Gilbert B, Lienhardt A, Palomera S, Barberis L, Borreda D. 
Fifty-six infants (aged 2 months to two years) with moderate to severe  diarrhea were entered in a comparative therapeutic trial of smectite versus placebo  or loperamide. Results showed that diarrhea resolved faster under smectite than under placebo and at least as fast under smectite as under loperamide.  Tolerance of smectite is excellent as a result of the lack of any effect on intestinal motility. 
11: Fortschr Med. 1991 Sep 10;109(26):528-32.  [Antacid therapy of upper  abdominal symptoms. Double-blind study on the effect and tolerance of 2 antacids in gastritis , esophagitis and functional upper abdominal symptoms] [Article in German] Lichtenstein H. 
In a randomized, multicenter, double-blind study involving a total of 97 patients, the effectiveness and tolerance of Gelofalk, a new type of antacid combination comprising smectite--a natural alum earth, the specific  molecular structure of which permits it to bind aggressive substances particularly well--aluminium hydroxide and magnesium hydroxide were investigated in comparison with a commercially available aluminium hydroxide antacid used by patients with gastritis, esophagitis and functional upper abdominal  complaints over a treatment period of 4 weeks. The buffering capacity of a daily dose  of Gelofalk was 135 mval, in the case of the reference antacid 210 mval. In  terms of pain relief, reduction of accompanying symptoms, and endoscopic healing properties, Gelofalk proved very effective. Because of its particular properties, the preparation proved significantly superior to an aluminium hydroxide suspension in the case of most test parameters, in particular pain relief, onset of effect and heartburn. Gelofalk was very well tolerated; constipation or diarrhea occurred in only 2 cases each. 
12: Pharmatherapeutica. 1988;5(4):256-60. A new suspension form of smectite (Liquid 'Diasorb') for the treatment of  acute diarrhoea: a randomized comparative study. Leber W. An open, multi-centre, general practice study was carried out in 80 patients with acute diarrhoea to compare the effectiveness and tolerability of  treatment with a liquid formulation of smectite, a hydrated aluminium-magnesium  silicate (Liquid 'Diasorb'), and loperamide. Patients were allocated at random to  receive one or other treatment for a maximum of 48 hours. Thirty-three of the  patients on the smectite preparation and 30 of those on loperamide had acute  diarrhoea of at least 24 hours but no longer than 48 hours in duration. Patients received  a daily dose of 6 to 9 g smectite or 8 to 12 mg loperamide, depending on the symptoms. Details of red and white cell counts, serum electrolyte  concentrations and stool culture for pathogens and parasites were recorded on entry and  after 1 week. The results, judged in terms of resolution of symptoms after 2 and 7  days, doctor and patient assessment of response to therapy, and incidence of side-effects, showed that both treatments were equally effective and well-tolerated. Two patients were withdrawn, 1 patient (Liquid 'Diasorb') because of lack of response and the other (loperamide) because of dryness of  the mouth and nausea. Laboratory parameters remained unchanged apart from a  slight decrease in leucocytes in both groups. 

Saludos, 

Martin 

Martin Canas
La Plata
(Argentina)