9[ucophAqi! Metformin Hydrochloride Classification GLUCOPHAGE (Metformin Hydrochloride) is an oral antidiabetic agent of the biguanide family.

Pharmacology GLUCOPHAGE is rapidly absorbed and excreted. The product is not metabolized and is excreted unchanged in the urine. GLUCOPHAGE lowers glycemia of the diabetic patient but not that of the normal human. Contrary to sulfonylureas hypoglycemia has never been reported at normal dows 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, GLUCOPHAGE 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 11 Uncomplicated maturity onwt diabetes without ketosis which cannot be controlled by dietary measures alone. 21 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 caw of primary or secondary sulfonylurea failure. Combined therapy of GLUCOPHAGE with a sulfonyluwa 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 t957. 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 the drug. GLUCOPHAGE maintains its activity during long treatment.

Adverse reactions Metallic taste in the mouth, epigastric discomfort, nausea and vomiting. Diarrhea and skin rasbes have been reported infrequently.

Precautions If vomiting occurs withdraw drug momentarily then resume dosage progressively. GLUCOPHAGE should be used cautiously in patients with Addison's 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 proceduws, a temporary change to insulin treatment is recommended. GLUCOPHAGE is contraindicated during pregnancies, jaundice, sevew liver and renal disorders. GLUCOPHAGE is contraindicated where tbere are pm-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 3to4gdaily. GLUCOPHAGE is best tolerated with meals. According to the results obtained, it may be required to increase the dose Iwithin the given limilsl; the increase should proceed slowly over a period of tO days to avoid gastro-intestinal discomfort.

Availability Tablets 10.5 gI white, round, convex, scored. Bottles of too and 500 tablets. F. fl @ F.) .2) kJ\.) Lh./

HARMACEUTIQUES LTEE HARMACEUTICALS LTD Laval Due. Canada.

repeated error: "Hockey, Canada's national sport". To ensure your journal maintains a high level of accuracy, it should be brought to everyone's attention that lacrosse is Canada's national sport. R.J. DOOLEY, MD

2400 Caning Ave. Ottawa, ON

Corticosteroids contained in Mexican cures for arthritis and asthma To the editor: During the past 6 months a number of Saskatchewan physicians and pharmacists have requested identification of unlabelled drugs obtained by patients from an "arthritis and asthmatic specialist clinic" in Mexicali, Mexico. It appears that word-of-mouth testimonials have persuaded some Saskatchewan residents suffering from arthritis and asthma to visit Mexico seeking a miracle cure. The prescriptions received at the clinic are never labelled and patients are told that the medications represent new advances in therapy kept out of the United States and Canada by "foolish" drug laws. The patients usually receive 6 months' supply of the "wonder drugs". Some have been assured by the Mexican specialist that cortisone is not being prescribed, but drug analysis by the Saskatchewan Dial Access Drug Information Service has shown that corticosteroids are indeed constituents of most of these treatment regimens (Table I). Those patients with rheumatoid arthritis are frequently treated with regimens containing diazepam, a corticosteroid and, in some instances, indomethacin. Patients with asthma usually receive a corticosteroid, diazepam and an antihistaminic (frequently dexchlorpheniramine). Such therapy may temporarily relieve the symptoms. This relief is primarily due to the corti-

costeroid, and it may take several months before the typical effects of corticosteroid therapy become apparent. Patients may then visit their local physician because of abnormal weight gain, fluid accumulation, or other symptoms attributable to the side effects of corticosteroids. In our analysis, chemical and instrumental analytic procedures were used. Tentative identification was made by comparing the ultraviolet spectra (run in acidic, basic or neutral solutions) with those recorded by Clarke1 or Beckstead and French,2 and positive identification was made by colour tests and by thin-layer and gas chromatography. No attempt was made to identify the particular corticosteroid or the potency of the dosage forms. The dimensions of the medications listed in Table I are approximations and are based on relatively few samples. A further problem is that various products may look similar, yet contain other ingredients. Therefore, this table should serve only as a guide for product identification and should be used with reservation. These patients usually hesitate to inform their local physician of their therapy, so the lack of medical supervision increases the probability of severe side effects developing. There is also the danger either that these patients' supply of medication may become exhausted or that patients may abruptly discontinue the therapy, which precipitates adrenal insufficiency. A large number of arthritic and asthmatic patients from various parts of the midwestern United States and California have been visiting this clinic in Mexicali during the past 2 years. We therefore believe it is important that this matter be brought to the attention of physicians across Canada, so that they may warn their patients of the

Table I-Chemical analysis and physical characteristics Diameter Physical form Description (mm) 8 Tablet, uncoated White, round, scored, fIat White, round, unscored, biconvex 6.5 Pinkish brown, round, unscored, 6.5 biconvex Green, round, scored, flat with bevel 8-8.5 Peach, round, scored, flat with bevel 8 Red, coated, elliptical 9.2 X 6.8 Tablet, coated Orange, coated, round, biconvex 9.2 8 Orange, coated, round, biconvex Pale green, coated, round, biconvex, 9.5 "SKF2" printed in red approx 18 Capsule Yellow, coated, no.2 hard x 6.2 gelatin capsule Yellow, uncoated, no. 3 hard approx 17 x5.5 gelatincapsule Liquid Clear syrup in 30-mi container

of Mexican clinic drugs Active ingredient Corticosteroid Corticosteroid Corticosteroid Diazepam Diazepam Dexchlorpheniramine Chlorpheniramine Chlorpheniramine Trifluoperazine tranylcypromine combination Indomethacin Indomethacin Corticosteroid

CMA JOURNAL/FEBRUARY 21, 1976/VOL 114 299

.Naprosyn®

pruritis, sweating and purpura. Angiodangers inherent in this type of therneurotic edema has been seen rarely. apy. Central Nervous System: Headache, dizziness, drowsiness, depression and fatigue J.L. BLACKBURN, PHARM D Brief Prescribing Information K.W. HINDMARSH, PH have been seen occasionally. Only a few Saskatchewan Dial Access DrugD Therapeutic Classification patients had to discontinue treatment beInformation Service do College of pharmacy cause of the severity of some of these Oral anti-inflammatory, analgesic and University of Saskatchewan complaints (headache, dizziness). Saskatoon, SK antipyretic agent. Hematologic Reactions: Although a def inReferences Indications ite causal relationship has not been 1. CLARKE ECG: Isolation and detection of The treatment of osteoarthritis, rheumatoid established, rare cases of thrombocytodrugs, in The Pharmaceutical Press, vol 1, arthritis and ankylosing (rheumatoid) penia or leucopenia have been reported. 1969; vol 2, 1975 2. BacKsm.n HD, FRENCH WN: Some Analytispondylitis. Cardiovascular Reactions: Dyspnea, mild cal Methods for Drugs Subject to Abuse, peripheral edema, ecchymoses and palpitaHealth and Welfare Canada, 1971 Contraindications tions have been encountered infrequently. Naprosyn shouldnot be given to patients with active peptic ulcer or active inflamma- Hepatic: One case of jaundice which reThe British NHS is not ail bad: appeared on challenge with Naprosyn has tory disease of the gastrointestinal tract. implications for Canada been reported, but definite relationship to It is also contraindicated for those who the drug has not been established. To the editor: In October 1975 I visited have shown a sensitivity to it and for Special Senses: A few eye abnormalities, patients in whom aspirin or other nonnine teaching centres in Great Britain including corneal changes, lens opacities, steroidal anti-inflammatory drugs induce while on the British Council course on macular degeneration and blurred vision the syndrome of asthma, rhinitis or organization of training and research in have been reported, but the relationship to u rticaria. anesthesia. By coincidence, the junior Naprosyn has not been established. Occasional instances of mild to moderately hospital doctors were beginning to take Warnings what they called "industrial action" to The safety of Naprosyn in pregnant, severe tinnitus have been seen. lactating or pediatric patients has not been Mouth and Throat Reactions: A few cases make their wishes known to the British established and, therefore, its use is not government. Although the problems of of severe sore throat have been observed, recommended under these conditions. these doctors and their overtime pay atbut the relationship to the drug has not been established. tracted headlines such as "Revolt of Precautions Laboratory Tests: It should be kept in mind the London Doctors", I was impressed Naprosyn should be given under close when bleeding times are determined that by the quiet and reasoned methods that supervision to patients prone to gastroNaprosyn decreases platelet aggregation British academic anesthetists had used intestinal tract irritation and to those with and prolongs bleeding time. Other laboradiverticulosis or a history of peptic ulcer. improve the training in anesthesia. to tory tests during Naprosyn therapy have Naprosyn may displace other albuminPerhaps these should be considered by shown sporadic abnormalities, but no bound drugs from their binding sites and Canadians. may lead to drug interactions. For example, definite trend was seen that would indicate In the centres we visited, research potential toxicity. patients receiving bishyd roxycoumarin, was an integral part of the teaching warfarin, hydantoin, sulfonamide or sulDosage and Administration program. The new Clinical Research fonylurea should be watched closely for The usual daily dosage of Naprosyn for Centre (CRC), built in conjunction with signs of overdosage or toxicity when osteoarthritis, rheumatoid arthritis and Northwick Park Hospital, Harrow, is Naprosyn is added to the regimen. Mild ankylosing spondylitis is 500 mg in divided funded by the Medical peripheral edema has been observed in a Research Coundoses. This may be increased to 750 mg or few cases. Consequently, patients with cil. The division CRC's of anesthesia decreased, depending on the response of compromised cardiac function should be the patient. Administration more frequently includes a physical chemist, biologist, kept under observation when taking than twice daily is not necessary. respiratory physician, three anesthetists, Naprosyn. The prescriber should be alert four technicians and other staff. The to the fact that anti-inflammatory, analgesic Dosage Forms National Health Service staff that and antipyretic effects of Naprosyn may mask the usual signs of infection. Naprosyn Naprosyn® is available as oval, biconvex provides service in anesthesia consists tablets, engraved N on one side and is excreted primarily in the urine and five consultant anesthetists, and of SYNTEX on the other. Each pale green should be administered with adequate the clinical staff supported by the NHS tablet contains 125mg naproxen. Bottles precaution to patients with diminished has access to the research environment. of 100 and 500 tablets. Each yellow tablet renal function. Naprosyn may produce Computing, animal service, radioisocontains 250mg naproxen. Bottles of 50 increased urinary values in the assay for and 250 tablets. tope, bioengineering and electron mi17-ketogenic steroids due to interaction croscopy facilities are shared with other between naproxen or its metabolites and Product Monograph available on request. m-dinitrobenzene used in this assay. It is, divisions. therefore, suggested that Naprosyn All the teaching centres we visited therapy be temporarily discontinued 48 had a good environment for anesthesia 1. Kogstad, 0.: Scand. J. Rheum. (Suppl.), hours before adrenal function tests are research. At Radcliffe Infirmary in Ox2:159,1973. performed. ford the anesthetic engineering section 2. Diamond, H. etal.: VI Pan Amer. Cong. Rheum. Diseases, Toronto, June 15, is involved in the design of instruments. Adverse Reactions 1974, in J. Clin. Pharmacol., 15:4,1975. The Nuffield Department in Oxford Gastrointestinal Tract: Infrequent bleeding 3. Hill, H. F. H. etal.: Proceedings of a can call on the services of about 20 with or without ulceration. In some cases, Symposium, London, 1973. the relationship to Naprosyn was difficult technicians with various backgrounds. to assess. Other adverse effects, in deThe teaching hospitals in Glasgow have creasing order of prevalence, were: access to the large department of medheartburn, constipation, abdominal pain, ical physics at the university, which innausea, diarrhea, dyspepsia and diverticcludes about 200 staff, some of whom ulitis. Only a few complaints were severe are attached to anesthesia departments enough to warrant discontinuation of in the city and are invaluable for carrytherapy. ing out research. Skin: Rashes have been relatively uncomAt some centres senior registrars are mon and generally cleared on withdrawal of the drug. Other reactions encountered, paid by the government through the Syntex Ltd. in decreasing order of frequency, were: Montreal, Quebec H4P 2B5 EE) university to train in some research

SYNTEX

302 CMA JOURNAL/FEBRUARY 21, 1976/VOL 114

Letter: Corticosteroids contained in Mexican cures for arthritis and asthma.

9[ucophAqi! Metformin Hydrochloride Classification GLUCOPHAGE (Metformin Hydrochloride) is an oral antidiabetic agent of the biguanide family. Pharma...
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