Granulocyte transfusions To the editor: I would like to draw your attention to certain statements in the recent editorial on granulocyte transfusions (Can Med Assoc J 113: 1020, 1975) - particularly two inaccurate statements and the conclusion. First, the editorial referred to a paper by Lowenthal and colleagues' that apparently illustrated the value of filtration leukapheresis: in fact, this paper deals exclusively with granulocyte procurement by the continuousflow blood cell separator. A second misstatement concerns transfusion reactions. It is correct to state that they "are more common with cells from leukemic donors". However, the "prior (my emphasis) treatment with steroids or etiocholanolone" and the use of "heparin and physiologic fluids" has absolutely nothing to do with the management of this complication. The former two agents are frequently given to normal donors to improve granulocyte transfusions.2'3 Etiocholanolone in particular would be of no use in the management of transfusion reactions and is contraindicated because it almost invariably provokes a febrile response.3 Heparin is used as an anticoagulant in all donors whether filtration or centrifugation techniques are being used, and its use is totally unrelated to the management of reactions. The use of physiologic fluids is neither reported (to my knowledge) nor rational when one considers that a major complication of transfusions is pulmonary edema. Finally, the severe reaction described in the editorial has been seen almost exclusively after transfusion of cells obContributions to the Correspondence section are welcomed and if considered suitable will be published as space permits. They should be typewritten double spaced and should not exceed 1½ pages in length.
tamed by the filtration technique, not by continuous-flow centrifugation.4 There are other statements that invite comment. One cannot deny that granulocytes "contain a large variety of antigens", both shared with other tissues and exclusive to granulocytes. However, these antigens are only of concern if the recipient has previously been sensitized to them and has preformed antibody. It is of the utmost importance, therefore, to search for such antibodies prior to transfusion to ensure both the safety and efficacy of the technique.5'6 The editorial glosses over the controversy concerning HL-A matching. Higby and colleagues presented no data to warrant the statement that the "outcome was not related to HL-A match" and they themselves state that the "importance of HL-A typing... is not yet clear".7 I would accept that statement, although some authors have been successful in relating response to degree of histocompatibility.8'9 Similarly, the risk of graft-v.-host disease has been understated. This has been well documented and has occasionally been fatal. Most centres are now irradiating cells before transfusion to avoid this dreaded complication.3'6 Finally, I take issue with the editorial's conclusion. If the technique referred to as showing "undoubted clinical efficacy" is filtration leukapheresis, then this statement is categorically incorrect. [The technique referred to was granulocyte transfusions in general Ed.] The filtration technique is not innocuous for the donor10 and often produces febrile and occasionally fatal reactions in the recipient.11 It may impair granulocyte function and post-transfusion granulocyte yields are poor.11 I might also add that, although the centrifugation technique suffers from few of the above drawbacks, the current
state of the art hardly allows one to proclaim its undoubted clinical efficacy. We and others are continuing to assess granulocyte transfusions in the supportive care of neutropenic patients, and while the evidence to date strongly supports their use, their role is still not firmly established. L. GROSSMAN, MD, CRCP (MED & HEM)
Director, cell separator unit Vancouver General Hospital Vancouver, BC
References I. LOWENTHAL
2.
3. 4.
5. 6. 7. 8. 9.
10.
11.
RM,
GROSSMAN
L,
GOLDMAN
JM, et al: Granulocyte transfusions in treatment of infections in patients with acute leukaemia and aplastic anaemia. Lancet 1: 353, 1975 HIosY DJ, MISHLita JM, RHOMBERO W, et al: The effect of a single or double dose of dexamethasone on granulocyte collection with the continuous flow centrifuge. Vox Sang 28: 243, 1975 HiGs'.' DJ, HENDERSON ES: Granulocyte transfusion therapy. Annu Rev Med 26: 289, 1975 SCHIFFER CA, BUcHHOLZ DH, AISNER J: Clinical experience with transfusion of granulocytes obtained by continuous flow filtration leukopheresis. Am J Med 58: 373, 1975 Bocos DR: Transfusion of neutrophils as prevention or treatment of infection in patients with neutropenia. N Engi J Med 290: 1055, 1974 GOLDMAN JM: Leucocyte separation and transfusion. Br J Haematol 28: 271, 1974 Hioav DJ, YAmS JW, HENDERSON ES, et al: Filtration leukapheresis for granulocyte transfusion therapy. N Engi I Med 292: 761, 1975 GRAW RG, HERzIG G, PERRY 5, et al: Normal granulocyte transfusion therapy. N Engi I Med 287: 368, 1972 HIOBY DJ, MISHLER JM, COHEN E, et al: Increased elevation of peripheral leukocyte counts by infusion of histocompatible granulocytes. Vox Sang 27: 186, 1974 BUcHHOLZ DH, SCHIFFER CA, WlaaNnt PH, et al: Granulocyte harvest for transfusion: donor response to repeated leukapheresis. Transfusion 15: 96, 1975 LEVINE AS, SCHIMPFF SC, GRAw RG, et al: Hematological malignancies and other marrow failure states: progress in the management of complicating infections. Semin Hematol 11: 141, 1974
Congenital absence of vas deferens To the editor: In the Journal of Dec. 13, 1975 I read once again about congenital absence of the vas deferens in association with vasectomy (Can Med Assoc J 113: 1022, 1975). Drs. Ho and Rao seemed somewhat surprised about such a finding and I
CMA JOURNAL/MARCH 20, 1976/VOL. 114 495
would like to bring to their attention the fact that pediatric surgeons have been aware that children with cystic fibrosis all lack a vas deferens. At a recent meeting of the American Pediatric Surgical Association it was reported that there is also a high frequency of renal anomalies on the side of the absent vas. In a paper in the Journal ot Pediatric Surgery Lukash, Zwiren and Andrews' discussed the significance of an absent vas deferens. They described how the vas develops from the mesonephric or wolffian duct, which forms from the pronephric duct in the original collecting portion of the primitive kidney; how the ureteric bud differentiates into the renal pelvis, ureters and collecting system of the true kidney; and finally, how a urogenital ridge forms, differentiating into the testicles or ovaries. An early disturbance in the area of the wolffian duct would affect formation of the ureteric bud as well as the vas, resulting in an anomalous vas with ipsilateral renal agenesis or dysgenesis. A disturbance at a later stage would affect the wolffian duct as it differentiated into the vas, but the kidney would be unaffected because the ureteric bud would already have differentiated. The testicle is almost always present in these instances because it originates from a different part of the urogenital ridge. The frequency of an absent vas in children undergoing hernia repair is about 1%. I refer those interested in such an anomaly to this well written paper by Lukash and colleagues. SIGMUND H. EIN, MD, FRCS[C] 250 Lawrence Ave. W Toronto, ON
Reference I. LUKASH T, ZWIREN LT, ANDREWS HL: Signi-
ficance of absent vas deferens at hernia repair in infants and children. J Pedjair Siug 10: 765, 1975
Length of blood pressure cuff To the editor: In a recent article (Can Med Assoc J 113: 103, 1975) Silverberg and associates stated "The mean blood pressures recorded in the physicians' offices averaged 23.7/11.1 mm Hg less than those recorded in the schools. One reason for this was that none of the physicians used pediatric cuffs, but these were required by 62.4% of the students at the screening. Hence, the intravascular blood pressure was probably underestimated in a number of cases in the physicians' offices." A different interpretation of the data is possible. Given the conditions under which blood pressure was determined, the values obtained in the schools may have been too high because the length of the bladder used was not adequate to
completely encircle the patient's arm. The authors considered cuff width to be ideal if it was 20% more than the diameter of the arm. However, the data presented by King' and Voors2 suggest that, while cuff width is a major factor, cuff length is of equal or more importance. Furthermore, there is no evidence that use of a cuff that is wider than the 20% recommendation by the American Heart Association3 results in an underestimation of the blood pressure. The data of Steinfeld, Alexander and Cohen4 suggest that it is difficult to underestimate the blood pressure because of a cuff that is too large, and supported the concept that adequate length of the cuff is important. I think that those of us who deal with children with widely variable arm circumference should keep in mind that an adequate length of the cuff may be more important than its width. MICHAEL D. BAILIE, MD, PH D
Associate professor Department of human development Michigan State University East Lansing, MI
References 1. KING GE: Errors in clinical measurement of blood pressure in obesity. Clin Sci 32: 223,
1967 2. VOORs Aw: Cuff bladder size in a blood pressure survey of children. Am J Epidemiol 101: 489, 1975 3. KIRKENDALL WM, BURTON AC, EPSTEIN FH, et al: Recommendations for human blood pressure determinations by spbygmomanometers. Circulation 36: 980, 1967 4. STEINFELD L, ALEXANDER H, COHEN ML: Updating spbygmomanometry. Am J Cardiol 33: 107, 1974
Minimizing the incidence of ASA-induced occult gastrointestinal bleeding To the editor: Recently Leist and Banwell' compiled a list of over 200 products containing acetylsalicylic acid (ASA) that are currently on the market. While some of these products are available on prescription only, others are available over the counter. Since the introduction of ASA tablets in the United States in 1915, this drug has become - and remains - the most widely used of all medications. It is, therefore, not surprising that such a large number of ASA-containing products are marketed. According to the United States Tariff Commission, in 1967 13.5 million kg of ASA were manufactured in the United States, enough to make approximately 113 million 5-gr tablets per day. In 1972 the American public consumed more than 9 million kg of ASA, or more than 75 million 5-gr tablets per day. Since the introduction of ASA into medical practice by Dreser,2 Wohlgemut3 and Witthauer,4 reports have appeared citing the adverse effects of ASA therapy. It has been established that repeated administration of ASA
496 CMA JOURNAL/MARCH 20, 1976/VOL. 114
9[ucophAq! Metformin Hydrochloride Classification CLUCOPHAGE (Metformin Hydrochloride) is an oral antidiabetic agent of the biguanide family.
Pharmacology CLUCOPHAGE is rapidly absorhed and excreted. The product is not metabolized and is excreted unchanged in the urine. GLUCOPHAGE lowers glycemia of the diabetic patient hut not that of the normal human. Contrary to sulfonylureas hypoglycemia has never been reported at normal doses in diabetic patients treated with GLUCOPHAGE alone. GLUCOPHAGE promotes an increase in the peripheral utilization of glucose and its activity is mediated through insulin. Therefore, CLUCOPHAGE improves the K coefficient of glucose assimilation and the coefficient of insulin efficiency. In the obese diabetic with hyperinsulinemia, GLUCOPHAGE is reported to normalize insulin output. This normalizing effect is concurrent to that of glycemia. During experiments, GLUCOPHAGE was shown to be devoid of any notable action in the body apart from its specific metabolic activity. Contrary to sulfonylureas, GLUCOPHAGE does not stimulate the pancreatic secretion of insulin.
Indications tI Uncomplicated maturity onset diabetes without ketosis which cannot be controlled by dietary measures alone. 2) GLUCOPHAGE is of particular value for the obese diabetic patient; besides its specific action on diabetes it often promotes an important loss of weight in the obese patient. 31 GLUCOPHAGE can also be administered, alone or combined with sulfonylureas, in the case of primary or secondary salfonylurea failure. Combined therapy of GLUCOPHAGE with a sulfonylurea can also be of considerable value in older diabetics where failure with either drug alone has occurred. This combined treatment can sometimes offer an alternative to insulin. The two compounds possibly act synergistically, the sulfonylurea promoting insulin release from pancreatic Beta cells and metformin potentiating its action on peripheral tissues. 41 Insulin adjuvant: The addition of GLUCOPHAGE to a regimen of insulin dependent patients may be of value, as the dose of insulin can often be reduced, in particular when insulin dosage is very high or when the patient is poorly controlled with insulin alone.
Clinical Use GLUCOPHAGE has been utilized throughout the world since 1957. Many clinical studies have demonstrated that GLUCOPHAGE is characterized as follows: As a sole medication GLUCOPHAGE does not bring about hypoglycemia in the normal human. Contrary to sulfonylureas, GLUCOPHAGE promotes loss of weight in the obese subject. Weight reduction is not related to dosage or to any anorexiant effect of tbe drug. GLUCOPHAGE maintains its activity during long treatment.
Adverse reactions Metallic taste in the mouth, epigastric discomfort, nausea and vomiting. Diarrhea and skin rashes have been reported infrequently.
Precautions If vomiting occurs withdraw drug momentarily then resume dosage progressively. GLUCOPHAGE should be used cautiously in patients with Addisons disease and in subjects intolerant to alcohol or sedatives. As with all other oral hypoglycemic agents, it is recommended that complete physical examinations including hepatic tests, blood counts and ophthalmoscopy be performed on a regular basis, in order to prevent or minimize long or short-term complications. Discontinue treatment in presence of a significant elevation of lactic acid levels in the blood.
Contraindications GLUCOPHAGE, used alone, is contraindicated in the case of ketotic, juvenile, insulin-deficient diabetes. GLUCOPHAGE is contraindicated in severe acidosis, coma and very unstable diabetes. During stress periods, such as severe infections, trauma or surgical procedures, a temporary change to insulin treatment is recommended. GLUCOPHAGE is contraindicated during pregnancies, jaundice, severe liver and renal disorders. GLUCOPHAGE is contraindicated where there are pre-existing complications peculiar to diabetes, for example: retinopathy, neuropathy, and nephropathy, and in latent and pre-diabetes.
Dosage and administration GLUCOPHAGE is administered orally. The usual dosage is 0.5 g three times a day, but it may be increased up to 3 to4 gdaily. GLUCOPHAGE is best tolerated with meals. According to the results obtained, it may be inquired to increase the dose within the given limits); the increase should proceed slowly over a period of todays to avoid gastro-intestinal discomfort.
Availability Tablets 10.5 gI white, round, convex, scored. Bottles of too and 500 tablets. ARMACEUTIQUES LTEE ARMACEUTICALS LTD L.©.O. LavaiQue. Canada
tamed by the filtration technique, not by continuous-flow centrifugation.4 There are other statements that invite comment. One cannot deny that granulocytes "contain a large variety of antigens", both shared with other tissues and exclusive to granulocytes. However, these antigens are only of concern if the recipient has previously been sensitized to them and has preformed antibody. It is of the utmost importance, therefore, to search for such antibodies prior to transfusion to ensure both the safety and efficacy of the technique.5'6 The editorial glosses over the controversy concerning HL-A matching. Higby and colleagues presented no data to warrant the statement that the "outcome was not related to HL-A match" and they themselves state that the "importance of HL-A typing... is not yet clear".7 I would accept that statement, although some authors have been successful in relating response to degree of histocompatibility.8'9 Similarly, the risk of graft-v.-host disease has been understated. This has been well documented and has occasionally been fatal. Most centres are now irradiating cells before transfusion to avoid this dreaded complication.3'6 Finally, I take issue with the editorial's conclusion. If the technique referred to as showing "undoubted clinical efficacy" is filtration leukapheresis, then this statement is categorically incorrect. [The technique referred to was granulocyte transfusions in general Ed.] The filtration technique is not innocuous for the donor10 and often produces febrile and occasionally fatal reactions in the recipient.11 It may impair granulocyte function and post-transfusion granulocyte yields are poor.11 I might also add that, although the centrifugation technique suffers from few of the above drawbacks, the current
state of the art hardly allows one to proclaim its undoubted clinical efficacy. We and others are continuing to assess granulocyte transfusions in the supportive care of neutropenic patients, and while the evidence to date strongly supports their use, their role is still not firmly established. L. GROSSMAN, MD, CRCP (MED & HEM)
Director, cell separator unit Vancouver General Hospital Vancouver, BC
References I. LOWENTHAL
2.
3. 4.
5. 6. 7. 8. 9.
10.
11.
RM,
GROSSMAN
L,
GOLDMAN
JM, et al: Granulocyte transfusions in treatment of infections in patients with acute leukaemia and aplastic anaemia. Lancet 1: 353, 1975 HIosY DJ, MISHLita JM, RHOMBERO W, et al: The effect of a single or double dose of dexamethasone on granulocyte collection with the continuous flow centrifuge. Vox Sang 28: 243, 1975 HiGs'.' DJ, HENDERSON ES: Granulocyte transfusion therapy. Annu Rev Med 26: 289, 1975 SCHIFFER CA, BUcHHOLZ DH, AISNER J: Clinical experience with transfusion of granulocytes obtained by continuous flow filtration leukopheresis. Am J Med 58: 373, 1975 Bocos DR: Transfusion of neutrophils as prevention or treatment of infection in patients with neutropenia. N Engi J Med 290: 1055, 1974 GOLDMAN JM: Leucocyte separation and transfusion. Br J Haematol 28: 271, 1974 Hioav DJ, YAmS JW, HENDERSON ES, et al: Filtration leukapheresis for granulocyte transfusion therapy. N Engi I Med 292: 761, 1975 GRAW RG, HERzIG G, PERRY 5, et al: Normal granulocyte transfusion therapy. N Engi I Med 287: 368, 1972 HIOBY DJ, MISHLER JM, COHEN E, et al: Increased elevation of peripheral leukocyte counts by infusion of histocompatible granulocytes. Vox Sang 27: 186, 1974 BUcHHOLZ DH, SCHIFFER CA, WlaaNnt PH, et al: Granulocyte harvest for transfusion: donor response to repeated leukapheresis. Transfusion 15: 96, 1975 LEVINE AS, SCHIMPFF SC, GRAw RG, et al: Hematological malignancies and other marrow failure states: progress in the management of complicating infections. Semin Hematol 11: 141, 1974
Congenital absence of vas deferens To the editor: In the Journal of Dec. 13, 1975 I read once again about congenital absence of the vas deferens in association with vasectomy (Can Med Assoc J 113: 1022, 1975). Drs. Ho and Rao seemed somewhat surprised about such a finding and I
CMA JOURNAL/MARCH 20, 1976/VOL. 114 495
would like to bring to their attention the fact that pediatric surgeons have been aware that children with cystic fibrosis all lack a vas deferens. At a recent meeting of the American Pediatric Surgical Association it was reported that there is also a high frequency of renal anomalies on the side of the absent vas. In a paper in the Journal ot Pediatric Surgery Lukash, Zwiren and Andrews' discussed the significance of an absent vas deferens. They described how the vas develops from the mesonephric or wolffian duct, which forms from the pronephric duct in the original collecting portion of the primitive kidney; how the ureteric bud differentiates into the renal pelvis, ureters and collecting system of the true kidney; and finally, how a urogenital ridge forms, differentiating into the testicles or ovaries. An early disturbance in the area of the wolffian duct would affect formation of the ureteric bud as well as the vas, resulting in an anomalous vas with ipsilateral renal agenesis or dysgenesis. A disturbance at a later stage would affect the wolffian duct as it differentiated into the vas, but the kidney would be unaffected because the ureteric bud would already have differentiated. The testicle is almost always present in these instances because it originates from a different part of the urogenital ridge. The frequency of an absent vas in children undergoing hernia repair is about 1%. I refer those interested in such an anomaly to this well written paper by Lukash and colleagues. SIGMUND H. EIN, MD, FRCS[C] 250 Lawrence Ave. W Toronto, ON
Reference I. LUKASH T, ZWIREN LT, ANDREWS HL: Signi-
ficance of absent vas deferens at hernia repair in infants and children. J Pedjair Siug 10: 765, 1975
Length of blood pressure cuff To the editor: In a recent article (Can Med Assoc J 113: 103, 1975) Silverberg and associates stated "The mean blood pressures recorded in the physicians' offices averaged 23.7/11.1 mm Hg less than those recorded in the schools. One reason for this was that none of the physicians used pediatric cuffs, but these were required by 62.4% of the students at the screening. Hence, the intravascular blood pressure was probably underestimated in a number of cases in the physicians' offices." A different interpretation of the data is possible. Given the conditions under which blood pressure was determined, the values obtained in the schools may have been too high because the length of the bladder used was not adequate to
completely encircle the patient's arm. The authors considered cuff width to be ideal if it was 20% more than the diameter of the arm. However, the data presented by King' and Voors2 suggest that, while cuff width is a major factor, cuff length is of equal or more importance. Furthermore, there is no evidence that use of a cuff that is wider than the 20% recommendation by the American Heart Association3 results in an underestimation of the blood pressure. The data of Steinfeld, Alexander and Cohen4 suggest that it is difficult to underestimate the blood pressure because of a cuff that is too large, and supported the concept that adequate length of the cuff is important. I think that those of us who deal with children with widely variable arm circumference should keep in mind that an adequate length of the cuff may be more important than its width. MICHAEL D. BAILIE, MD, PH D
Associate professor Department of human development Michigan State University East Lansing, MI
References 1. KING GE: Errors in clinical measurement of blood pressure in obesity. Clin Sci 32: 223,
1967 2. VOORs Aw: Cuff bladder size in a blood pressure survey of children. Am J Epidemiol 101: 489, 1975 3. KIRKENDALL WM, BURTON AC, EPSTEIN FH, et al: Recommendations for human blood pressure determinations by spbygmomanometers. Circulation 36: 980, 1967 4. STEINFELD L, ALEXANDER H, COHEN ML: Updating spbygmomanometry. Am J Cardiol 33: 107, 1974
Minimizing the incidence of ASA-induced occult gastrointestinal bleeding To the editor: Recently Leist and Banwell' compiled a list of over 200 products containing acetylsalicylic acid (ASA) that are currently on the market. While some of these products are available on prescription only, others are available over the counter. Since the introduction of ASA tablets in the United States in 1915, this drug has become - and remains - the most widely used of all medications. It is, therefore, not surprising that such a large number of ASA-containing products are marketed. According to the United States Tariff Commission, in 1967 13.5 million kg of ASA were manufactured in the United States, enough to make approximately 113 million 5-gr tablets per day. In 1972 the American public consumed more than 9 million kg of ASA, or more than 75 million 5-gr tablets per day. Since the introduction of ASA into medical practice by Dreser,2 Wohlgemut3 and Witthauer,4 reports have appeared citing the adverse effects of ASA therapy. It has been established that repeated administration of ASA
496 CMA JOURNAL/MARCH 20, 1976/VOL. 114
9[ucophAq! Metformin Hydrochloride Classification CLUCOPHAGE (Metformin Hydrochloride) is an oral antidiabetic agent of the biguanide family.
Pharmacology CLUCOPHAGE is rapidly absorhed and excreted. The product is not metabolized and is excreted unchanged in the urine. GLUCOPHAGE lowers glycemia of the diabetic patient hut not that of the normal human. Contrary to sulfonylureas hypoglycemia has never been reported at normal doses in diabetic patients treated with GLUCOPHAGE alone. GLUCOPHAGE promotes an increase in the peripheral utilization of glucose and its activity is mediated through insulin. Therefore, CLUCOPHAGE improves the K coefficient of glucose assimilation and the coefficient of insulin efficiency. In the obese diabetic with hyperinsulinemia, GLUCOPHAGE is reported to normalize insulin output. This normalizing effect is concurrent to that of glycemia. During experiments, GLUCOPHAGE was shown to be devoid of any notable action in the body apart from its specific metabolic activity. Contrary to sulfonylureas, GLUCOPHAGE does not stimulate the pancreatic secretion of insulin.
Indications tI Uncomplicated maturity onset diabetes without ketosis which cannot be controlled by dietary measures alone. 2) GLUCOPHAGE is of particular value for the obese diabetic patient; besides its specific action on diabetes it often promotes an important loss of weight in the obese patient. 31 GLUCOPHAGE can also be administered, alone or combined with sulfonylureas, in the case of primary or secondary salfonylurea failure. Combined therapy of GLUCOPHAGE with a sulfonylurea can also be of considerable value in older diabetics where failure with either drug alone has occurred. This combined treatment can sometimes offer an alternative to insulin. The two compounds possibly act synergistically, the sulfonylurea promoting insulin release from pancreatic Beta cells and metformin potentiating its action on peripheral tissues. 41 Insulin adjuvant: The addition of GLUCOPHAGE to a regimen of insulin dependent patients may be of value, as the dose of insulin can often be reduced, in particular when insulin dosage is very high or when the patient is poorly controlled with insulin alone.
Clinical Use GLUCOPHAGE has been utilized throughout the world since 1957. Many clinical studies have demonstrated that GLUCOPHAGE is characterized as follows: As a sole medication GLUCOPHAGE does not bring about hypoglycemia in the normal human. Contrary to sulfonylureas, GLUCOPHAGE promotes loss of weight in the obese subject. Weight reduction is not related to dosage or to any anorexiant effect of tbe drug. GLUCOPHAGE maintains its activity during long treatment.
Adverse reactions Metallic taste in the mouth, epigastric discomfort, nausea and vomiting. Diarrhea and skin rashes have been reported infrequently.
Precautions If vomiting occurs withdraw drug momentarily then resume dosage progressively. GLUCOPHAGE should be used cautiously in patients with Addisons disease and in subjects intolerant to alcohol or sedatives. As with all other oral hypoglycemic agents, it is recommended that complete physical examinations including hepatic tests, blood counts and ophthalmoscopy be performed on a regular basis, in order to prevent or minimize long or short-term complications. Discontinue treatment in presence of a significant elevation of lactic acid levels in the blood.
Contraindications GLUCOPHAGE, used alone, is contraindicated in the case of ketotic, juvenile, insulin-deficient diabetes. GLUCOPHAGE is contraindicated in severe acidosis, coma and very unstable diabetes. During stress periods, such as severe infections, trauma or surgical procedures, a temporary change to insulin treatment is recommended. GLUCOPHAGE is contraindicated during pregnancies, jaundice, severe liver and renal disorders. GLUCOPHAGE is contraindicated where there are pre-existing complications peculiar to diabetes, for example: retinopathy, neuropathy, and nephropathy, and in latent and pre-diabetes.
Dosage and administration GLUCOPHAGE is administered orally. The usual dosage is 0.5 g three times a day, but it may be increased up to 3 to4 gdaily. GLUCOPHAGE is best tolerated with meals. According to the results obtained, it may be inquired to increase the dose within the given limits); the increase should proceed slowly over a period of todays to avoid gastro-intestinal discomfort.
Availability Tablets 10.5 gI white, round, convex, scored. Bottles of too and 500 tablets. ARMACEUTIQUES LTEE ARMACEUTICALS LTD L.©.O. LavaiQue. Canada
