INDICATIONS: Sustained moderate through severe hypertension. DOSAGE SUMMARY: Start usually with 250 mg two or three times daily during the first 48 hours, thereafter adjust at intervals of not less than two days according to the patient's response. Maximal daily dosage is 3.0 g of methyldopa. In the presence of impaired renal function smaller doses may be needed. Syncope in older patients has been related to an increased sensitivity in those patients with advanced arteriosclerotic vascular disease and may be avoided by reducing the dose. Tolerance may occur occasionally between the second and third month after initiating therapy. Effectiveness can frequently be restored by increasing the dose or adding a thiazide. CONTRAINDICATIONS: Active hepatic disease such as acute hepatitis and active cirrhosis; known sensitivity to methyldopa; unsuitable in mild or labile hypertension responsive to mild sedation or thiazides alone; pheochromocytoma; pregnancy. Use cautiously if there is a history of liver disease or dysfunction. PRECAUTIONS: Acquired hemolytic anemia has occurred rarely. Hemoglobin and/or hematocrit determinations should be performed when anemia is suspected. If anemia is present, determine if hemolysis is present. Discontinue methyldopa on evidence of hemolytic anemia. Prompt remission usually results on discontinuation alone or the initiation of adrenocortical steroids. Rarely, however, fatalities have occurred. A positive direct Coombs test has been reported in some patients on continued therapy with methyldopa, the exact mechanism and significance of which is not established. Incidence has varied from 10 to 20%. If a positive test is to develop it usually does within 12 months following start of therapy. Reversal of positive test occurs within weeks to months after discontinuation of the drug. Prior knowledge of this reaction will aid in cross matching blood for transfusion. This may result in incompatible minor cross match. If the indirect Coombs test is negative, transfusion with otherwise compatible blood may be carried out. If positive, advisability of transfusion should be determined by a hematologist or expert in transfusion problems. Reversible leukopenia with primary effect on granulocytes has been seen rarely. Rare cases of clinical agranulocytosis have been reported. Granulocyte and leukocyte counts returned promptly to normal on discontinuance of drug. Occasionally fever has occurred within the first three weeks of therapy, sometimes associated with eosinophilia or abnormalities in one or more liver function tests. jaundice, with or without fever, may occur also, with onset usually within first 2 or 3 months of therapy. Rare cases of fatal hepatic necrosis have been reported. Liver biopsies in several patients with liver dysfunction showed a microscopic focal necrosis compatible with drug hypersensitivity. Determine liver function, leukocyte and differential blood counts at intervals during the first six to twelve weeks of therapy or whenever unexplained fever may occur. Discontinue if fever, abnormalities in liver function tests, or jaundice occur. Methyldopa may potentiate action of other antihypertensive drugs. Foldow patients carefully to detect side reactions or unusual manifestations of drug idiosyncrasy. Patients may require reduced doses of anesthetics when on ALDOMET*. If hypotension does occur during anesthesia, it usually can be controlled by vasopressors. The adrenergic receptors remain sensitive during treatment with methyldopa. Hypertension occasionally noted after dialysis in patients treated with ALDOMET* may occur because the drug is removed by this procedure. Rarely involuntary choreoathetotic movements have been observed during therapy with methyldopa in patients with severe bilateral cerebrovascular disease. Should these movements occur, discontinue therapy. Fluorescence in urine samples at same wave lengths as catecholamines may be reported as urinary catecholamines. This will interfere with the diagnosis of pheochromocytoma. Methyldopa will not serve as a diagnostic test for pheochromocytoma. Usage in Pregnancy: Because clinical experience and follow-up studies in pregnancy have been limited, the use of methyldopa when pregnancy is present or suspected requires that the benefits of the drug be weighed against the possible hazards to the fetus. ADVERSE REACTIONS: Cardiovascular: Angina pectoris may be aggravated; reduce dosage if symptoms of orthostatic hypotension occur; bradycardia occurs occasionally. Neurological: Symptoms associated with effective lowering of blood pressure occasionally seen include dizziness, lightheadedness, and symptoms of cerebrovascular insufficiency. Sedation, usually transient, seen during initial therapy or when dose is increased. Similarly, headache, asthenia, or weakness may be noted as early, but transient symptoms. Rarely reported: paresthesias, parkinsonism, psychic disturbances including nightmares, reversible mild psychoses or depression, and a single case of bilateral Bell's palsy. Gastrointestinal: Occasional reactions generally relieved by decrease in dosage: mild dryness of the mouth and gastrointestinal symptoms including distention, constipation, flatus, and diarrhea; rarely, nausea and vomiting. Hematological: Positive direct Coombs test, acquired hemolytic anemia, le&kopenia and rare cases of thrombocytopenia. Toxic and Allergic: Occasional drug related fever and abnormal liver function studies with jaundice and hepatocellular damage (see PRECAUTIONS) and a rise in BUN. Rarely, skin rash, sore tongue or "black tongue", pancreatitis and inflammation of the salivary glands. Endocrine and Metabolic: Rarely, breast enlargement, lactation, impotence, decreased libido; weight gain and edema which may be relieved by administering a thiazide diuretic. If edema progresses or signs of pulmonary congestion appear, discontinue drug. Miscellaneous: Occasionally nasal stuffiness, mild arthralgia and myalgia; rarely, darkening of urine after voiding. Full prescribing information available on request. How Supplied: Tablets ALDOMET* are yellow, film-coated, biconvex shaped tablets, supplied as follows: Ca 8737-each tablet containing 125 mg of methyldopa, marked MSD 135 on one side, supplied in bottles of 100 and 1,000. Ca 3290-each tablet containing 250 mg of methyldopa, marked MSD 401 on one side, supplied in bottles of 100 and 1,000. Ca 8733-each tablet containing 500 mg of methyldopa, marked MSD 516 on one side, supplied in bottles of 100 and 250. Also available: Ca 3293-Injection ALDOMET* Ester hydrochloride, a clear colourless solution containing 250 mg methyldopate hydrochloride per 5 ml, supplied in 5 ml ampoules. *Trademark (MC-1 20)
I MERCK £9 I SHARP I & DOHME CANADA LIMITED POINTE CLAIRE, QUEBEC
best explanation for the rather rapid apparent decrease in incidence of taeniasis. Whatever the history, the outbreak of taeniasis that appeared suddenly three quarters of a century ago disappeared without trace. R.D.P. EATON, PH D, MB, .H B Northern medical research unit Medical services Charles Camsell Hospital Edmonton, Alta.
Health manpower statistics To the editor: In response to the article by Dr. C.B. Stewart, "How accurate and relevant are physician manpower statistics?" (Can Med Assoc J 114: 835, 1976), I am pleased to note that the health manpower statistics issued by Health and Welfare Canada have attracted sufficient interest and careful scrutiny to give rise to this challenging article. Although I believe Dr. Stewart has tended to misconstrue the nature and purpose of our published data, he has provided some useful comments that will be very helpful to those preparing future publications on health manpower statistics. Regarding Dr. Stewart's contention that the data published in the "Canada Health Manpower Inventory" (1974) is irrelevant, I might point out that the publication was never intended to meet all possible needs for health manpower statistics. As implied in the title, it was designed to provide inventory-type information on total manpower resources, including those actually in practice, those potentially available to provide services and those undergoing training. Dr. Stewart has asserted that the figures on "active physicians" published in the inventory convey the misleading impression that the data refer to numbers of clinical practitioners in full-time practice. I can only reply that we intended the term to refer to physicians "active" in a professional sense, excluding only physicians who are retired because of age or who are engaged in activities totally unrelated to their medical qualifications. Tables and footnotes in the inventory make it clear that the data included not only physicians in clinical practice, but also physicians engaged in teaching, research, administration etc., as well as interns and residents. I agree with Dr. Stewart's observation regarding the importance for manpower planning of accurate information on full-time physicians in clinical practice. As a matter of fact, this department and Statistics Canada have attempted for some time to establish a physician manpower data bank that would include the necessary information. Cooperation by other partners in
CMA JOURNAL/NOVEMBER 20, 1976/VOL. 115 981
the project (and consequently its progress) has been limited until now. the absence of appropriate information we can only estimate the number of full-time-equivalent physicians in clinical practice by means of various proxy measures. One approach is based upon payment data of provincial medical care insurance programs on fee- and non-fee-for-service practitioners and upon hospital statistics on full-time, paid medical staff. In addition, however, medical schools must also meet the needs of society in medical health administration, medical research and the variety of other related activities that do not involve direct services to patients. Requirements in all these areas have to be taken into consideration when planning the appropriate supply of trained physicians needed in Canada. The overall ratio of "active physicians" to population, which includes physicians involved in these related areas as well as those rendering clinical services, is needed as a comprehensive standard of measurement. Accordingly, I am unable to accept Dr. Stewart's statement that the use of such figures represents an overestimation of existing physician manpower in relation to the true needs of Canadians. I hope the above will make it clear
that Dr. Stewart's references to political pressure and "slanted statistics" have no relevance to the physician manpower statistics published by Health and Welfare Canada. W.A. MENNIE I)irector Health economics and statistics division Health and Welfare Canada
To the editor: The assurance that manpower statistics have not been intentionally slanted may be comforting to some. However, I still contend that unintentional slanting is equally to be deplored. The director and staff of the former health manpower directorate should be criticized not because some people have misused the statistics from the inventory - as they have - but for failure to follow the most elementary rules of statistical analysis and epidemiologic research, which could hardly fail to result in misinterpretation. I did not say all data published in the "Canada Health Manpower Inventory" (1974) were irrelevant, but I do still question the relevance of including nonclinicians in the population:physician ratios. Size of population is not the main factor determining their number. Mr. Mennie states that the inventory was not intended to refer to numbers
'. I 5 5
2.
of practitioners in full-time clinical practice but all physicians "active" in a professional sense. I contend that the definition "physician", as contained in the inventory and published in full in my paper, does describe clinicians or practising doctors. Furthermore, the inventory made a perfectly valid reduction in the total number of licensed dentists and the ratio of licensed dentists to population (Tables 5.1 and 5.2) in order to obtain a better estimate of the number and ratio of "active" dentists to population (Tables 5.3 and 5.4). The reduced figures for "active" dentists excluded those who are part-time, semiretired or engaged in nonclinical work. On the contrary, "active physician,. - a similar term, almost certain to be interpreted in the same way - included all part-time clinicians, retired practitioners who retained licensure, a relatively large number of physicians in administration, research and education, and all postgraduate students still in training. I agree with Mr. Mennie that one could dig out the information from the inventory, as I did. But I also know that most health care planners in Canada accepted the ratio of physicians to population as an official and accurate figure on which planning could
GravoIhastheansv.r.
For the prevention end treatment of postoperative nausea and vomiting, consider Gravol parenGraveli/rnis inavallabie (dimenhydrinate). ampoules terai forms: 50 mg/mi 1 and 2 inmiseveral and 5 ml vials and 10mg/mi i/v inS ml ampouies. Gravoi (dimenhydrinate) is also avallabie in the foilowing forms: 50 mg tablets. 75 mg long-acting capsules. 100 mg adult suppositories. 15 mg/5 ml liquid in 75 ml plastic containere. 50mg pediatric suppositories.
GRAVOL
Canada's most widely used antinauseant.
s.pp.sito.Is s.pposftmI.s
I 982 CMA JOURNAL/NOVEMBER 20, 1976/VOL. 115
.aps..I.s
I MERCK £9 I SHARP I & DOHME CANADA LIMITED POINTE CLAIRE, QUEBEC
best explanation for the rather rapid apparent decrease in incidence of taeniasis. Whatever the history, the outbreak of taeniasis that appeared suddenly three quarters of a century ago disappeared without trace. R.D.P. EATON, PH D, MB, .H B Northern medical research unit Medical services Charles Camsell Hospital Edmonton, Alta.
Health manpower statistics To the editor: In response to the article by Dr. C.B. Stewart, "How accurate and relevant are physician manpower statistics?" (Can Med Assoc J 114: 835, 1976), I am pleased to note that the health manpower statistics issued by Health and Welfare Canada have attracted sufficient interest and careful scrutiny to give rise to this challenging article. Although I believe Dr. Stewart has tended to misconstrue the nature and purpose of our published data, he has provided some useful comments that will be very helpful to those preparing future publications on health manpower statistics. Regarding Dr. Stewart's contention that the data published in the "Canada Health Manpower Inventory" (1974) is irrelevant, I might point out that the publication was never intended to meet all possible needs for health manpower statistics. As implied in the title, it was designed to provide inventory-type information on total manpower resources, including those actually in practice, those potentially available to provide services and those undergoing training. Dr. Stewart has asserted that the figures on "active physicians" published in the inventory convey the misleading impression that the data refer to numbers of clinical practitioners in full-time practice. I can only reply that we intended the term to refer to physicians "active" in a professional sense, excluding only physicians who are retired because of age or who are engaged in activities totally unrelated to their medical qualifications. Tables and footnotes in the inventory make it clear that the data included not only physicians in clinical practice, but also physicians engaged in teaching, research, administration etc., as well as interns and residents. I agree with Dr. Stewart's observation regarding the importance for manpower planning of accurate information on full-time physicians in clinical practice. As a matter of fact, this department and Statistics Canada have attempted for some time to establish a physician manpower data bank that would include the necessary information. Cooperation by other partners in
CMA JOURNAL/NOVEMBER 20, 1976/VOL. 115 981
the project (and consequently its progress) has been limited until now. the absence of appropriate information we can only estimate the number of full-time-equivalent physicians in clinical practice by means of various proxy measures. One approach is based upon payment data of provincial medical care insurance programs on fee- and non-fee-for-service practitioners and upon hospital statistics on full-time, paid medical staff. In addition, however, medical schools must also meet the needs of society in medical health administration, medical research and the variety of other related activities that do not involve direct services to patients. Requirements in all these areas have to be taken into consideration when planning the appropriate supply of trained physicians needed in Canada. The overall ratio of "active physicians" to population, which includes physicians involved in these related areas as well as those rendering clinical services, is needed as a comprehensive standard of measurement. Accordingly, I am unable to accept Dr. Stewart's statement that the use of such figures represents an overestimation of existing physician manpower in relation to the true needs of Canadians. I hope the above will make it clear
that Dr. Stewart's references to political pressure and "slanted statistics" have no relevance to the physician manpower statistics published by Health and Welfare Canada. W.A. MENNIE I)irector Health economics and statistics division Health and Welfare Canada
To the editor: The assurance that manpower statistics have not been intentionally slanted may be comforting to some. However, I still contend that unintentional slanting is equally to be deplored. The director and staff of the former health manpower directorate should be criticized not because some people have misused the statistics from the inventory - as they have - but for failure to follow the most elementary rules of statistical analysis and epidemiologic research, which could hardly fail to result in misinterpretation. I did not say all data published in the "Canada Health Manpower Inventory" (1974) were irrelevant, but I do still question the relevance of including nonclinicians in the population:physician ratios. Size of population is not the main factor determining their number. Mr. Mennie states that the inventory was not intended to refer to numbers
'. I 5 5
2.
of practitioners in full-time clinical practice but all physicians "active" in a professional sense. I contend that the definition "physician", as contained in the inventory and published in full in my paper, does describe clinicians or practising doctors. Furthermore, the inventory made a perfectly valid reduction in the total number of licensed dentists and the ratio of licensed dentists to population (Tables 5.1 and 5.2) in order to obtain a better estimate of the number and ratio of "active" dentists to population (Tables 5.3 and 5.4). The reduced figures for "active" dentists excluded those who are part-time, semiretired or engaged in nonclinical work. On the contrary, "active physician,. - a similar term, almost certain to be interpreted in the same way - included all part-time clinicians, retired practitioners who retained licensure, a relatively large number of physicians in administration, research and education, and all postgraduate students still in training. I agree with Mr. Mennie that one could dig out the information from the inventory, as I did. But I also know that most health care planners in Canada accepted the ratio of physicians to population as an official and accurate figure on which planning could
GravoIhastheansv.r.
For the prevention end treatment of postoperative nausea and vomiting, consider Gravol parenGraveli/rnis inavallabie (dimenhydrinate). ampoules terai forms: 50 mg/mi 1 and 2 inmiseveral and 5 ml vials and 10mg/mi i/v inS ml ampouies. Gravoi (dimenhydrinate) is also avallabie in the foilowing forms: 50 mg tablets. 75 mg long-acting capsules. 100 mg adult suppositories. 15 mg/5 ml liquid in 75 ml plastic containere. 50mg pediatric suppositories.
GRAVOL
Canada's most widely used antinauseant.
s.pp.sito.Is s.pposftmI.s
I 982 CMA JOURNAL/NOVEMBER 20, 1976/VOL. 115
.aps..I.s
