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ORAL CONTRACEPTIVES CONTAINING ŒSTROGENS
1369 raised erythrocyte-sedimentation rate (E.S.R.) of 76 mm. in 1st hour (Westergren), raised serum-glutamic-oxaloacetic transaminase (98 units), raised serum-alkaline-phosphatase
had been given which might have explained the symptoms.4 There remains the possibility, suggested by Crampton,5 that the side-effects were due to the bactericidal agent,
a
methyl hydroxybenzoate, used as a preservative. It seems reasonable to employ the preparation of lignocaine which
(31 King-Armstrong units), normal serum-amylase, and a normal serum-protein electrophoretic pattern. A liver biopsy was attempted, but unfortunately no liver tissue was obtained. Nitrofurantoin was immediately
does
not
contain this agent.
Department of Cardiology, Sully Hospital, Glamorganshire.
MUHAMMAD ILYAS DAVID OWENS GEORGE KVASNICKA.
ORAL CONTRACEPTIVES CONTAINING ŒSTROGENS SIR,-A preliminary communication from the Committee on Safety of Drugs has just been sent to all doctors in the United Kingdom. The text is as follows: "
Approximately half the oral contraceptives presented in the United Kingdom contain 75 microgrammes or more of oestrogen in the form of either mestranol or ethinyloestradiol ; the remainder contain only 50 microgrammes. " Reports of suspected adverse reactions received by the Committee on Safety of Drugs now provide evidence that the incidence of thrombo-embolism is higher among women taking preparations containing larger doses of oestrogen than among those taking preparations containing the smaller dose. " The Committee has no evidence that oral contraceptives containing 50 microgrammes of oestrogen are less effective than the others and recommends that oral contraceptives containing the smaller dose of oestrogen should normally be prescribed." The Committee has no evidence on which to base any advice about the incidence of thromboembolism during the use of any oral contraceptive containing progestogen alone. The relation between the use of oral contraceptives and thromboembolism has been well established, but the Committee is of the opinion that the risk of this complication is less with the lower oestrogen dose. The Committee is not suggesting that any of these preparations should not be available for the treatment of gynaecological disorders, and the early warning refers solely to their use as oral contraceptives. Arrangements had been made to ensure that the profession was informed before any public announcement was made. Unfortunately, premature Press publicity necessitated an urgent public announcement in order to allay undue anxiety and to allow of informed Press comment. The Committee regrets that this should have been necessary and apologises to the profession as a whole that things have occurred in this inappropriate order through no fault of its own.
None of the work which has been undertaken would have been possible without the help of a large number of the profession, and the Committee is very grateful for that collaboration. It would, however, urge an increased vigilance on the profession as a whole in relation to adverse reactions from contraceptive medication, and asks that the Committee should be informed at the earliest opportunity of adverse reactions. It is only by this full collaboration that drug-safety problems can be identified and early
warnings given. Queen Anne’s Mansions, Queen Anne’s Gate, London S.W.1.
E. F. SCOWEN Chairman, Committee Safety of Drugs.
on
HEPATIC REACTION TO NITROFURANTOIN SIR,-We have recently seen a woman of 57 who, following 2 weeks’ therapy with nitrofurantoin for chronic pyelonephritis, developed a diffuse pruritic maculopapular rash on both legs, and generalised myalgias and arthralgias. These were associated with absolute eosinophilia (1014 eosinophils per c.mm.), a normal total-serum-bilirubin of 0-5 mg. per 100 ml. (direct van den Bergh reaction negative), 4. 5.
Smith, W. G. Lancet, 1968, ii, 397. Crampton, R. S. J. Am. med. Ass. 1968, 205,
803.
withdrawn and the reaction subsided. Clinical and biochemical features returned to normal within 7 days, except that the E.s.R. remained raised at 47 mm. per hour. In view of the clinical improvement and the emotional instability of the patient, it was not considered justifiable to repeat the liver biopsy. This experience prompted us to survey published reports during the past decade (1960-69) on nitrofurantoin toxicity, with special reference to hepatic complications. We found eighty-four references on the subject. Over 50% of the reported complications were related to the lungs (pneumonias, pulmonary infiltrations, &c.) and peripheral nerves (polyneuritis). The remainder included anaphylaxis, megaloblastic and haemolytic anxmias, skin lesions, eosinophilia, dental disorders, and cardiac arrhythmias. Only six cases 1-6 of non-haemolytic jaundice were discovered, the first having been reported by Ernaelsteen and Williams in 1961.1 In four 1-4 of these there was evidence of intrahepatic cholestasis; in onethe liver-function tests were abnormal and toxic hepatitis was suspected, but liver biopsy was not done because,of a hxmorrhagic diathesis. In the sixth case6 a liver biopsy specimen and liver-function tests were normal, despite a raised serum-bilirubin. Five out of six of these cases of liver involvement were associated with jaundice. Since our patient had clinical and biochemical evidence of liver involvement without jaundice, it seemed worthwhile reporting this case briefly. Department of Pathology and Division of Gastroenterology, St. Michael’s Hospital, ARVIND G. BHAGWAT University of Toronto, RALPH E. WARREN. Toronto, Ontario. EXPERT WITNESSES Dr. RAYMOND GREENE writes: " In the course of my recovery from a painful illness I have examined descriptions of the symptoms in a number of standard textbooks. All of them were completely inadequate. It occurred to me that a book consisting of descriptions of diseases, written by doctors who have suffered from them, might be of value. Heinemann Medical Books Ltd. propose to publish such a book if sufficient material is available. I should be glad if any of your readers who have had a disorder which might be of interest would write a detailed description of the illness and the effects of treatment, and send the manuscript to me c/o William Heinemann Medical Books Ltd., 23 Bedford Square, London W.C.1." HELP FOR BIAFRAN CHILDREN Dr. WENDY SAVAGE writes: " I should like to appeal through your columns for help for the Centre Medicale, Leconi, Republic of Gabon. This centre has been set up, with the aid of the Gabonese Government, primarily to treat Biafran children (this occasionally includes their mothers as well). The Biafran doctor in charge, Onyemara (Dick) Onyeaso, is asking for assistance: he needs money to buy drugs (paediatric sedatives, antibiotics, and vita-
mins)
and equipment (especially extractor, and I.U.C.D.S).
vacuum
an
E.M.O.
machine,
a
I worked with Dr.
1. Ernaelsteen, D., Williams, R. Gastroenterology, 1961, 41, 590. 2. Cook, G. C., Sherlock, S. Lancet, 1965, i, 175. 3. Jokela, S. Gastroenterology, 1967, 53, 306. 4. Wasowska, T., Krus, S. Pol. med. J. 1968, 7, 322. 5. Murphy, K. J., Innis, M. D. J. Am. med. Ass. 1968, 204, 396. 6. Jowers, L. V., Shannon, S. R. Jl. S. Carol. med. Ass. 1967, 63, 357.
had been given which might have explained the symptoms.4 There remains the possibility, suggested by Crampton,5 that the side-effects were due to the bactericidal agent,
a
methyl hydroxybenzoate, used as a preservative. It seems reasonable to employ the preparation of lignocaine which
(31 King-Armstrong units), normal serum-amylase, and a normal serum-protein electrophoretic pattern. A liver biopsy was attempted, but unfortunately no liver tissue was obtained. Nitrofurantoin was immediately
does
not
contain this agent.
Department of Cardiology, Sully Hospital, Glamorganshire.
MUHAMMAD ILYAS DAVID OWENS GEORGE KVASNICKA.
ORAL CONTRACEPTIVES CONTAINING ŒSTROGENS SIR,-A preliminary communication from the Committee on Safety of Drugs has just been sent to all doctors in the United Kingdom. The text is as follows: "
Approximately half the oral contraceptives presented in the United Kingdom contain 75 microgrammes or more of oestrogen in the form of either mestranol or ethinyloestradiol ; the remainder contain only 50 microgrammes. " Reports of suspected adverse reactions received by the Committee on Safety of Drugs now provide evidence that the incidence of thrombo-embolism is higher among women taking preparations containing larger doses of oestrogen than among those taking preparations containing the smaller dose. " The Committee has no evidence that oral contraceptives containing 50 microgrammes of oestrogen are less effective than the others and recommends that oral contraceptives containing the smaller dose of oestrogen should normally be prescribed." The Committee has no evidence on which to base any advice about the incidence of thromboembolism during the use of any oral contraceptive containing progestogen alone. The relation between the use of oral contraceptives and thromboembolism has been well established, but the Committee is of the opinion that the risk of this complication is less with the lower oestrogen dose. The Committee is not suggesting that any of these preparations should not be available for the treatment of gynaecological disorders, and the early warning refers solely to their use as oral contraceptives. Arrangements had been made to ensure that the profession was informed before any public announcement was made. Unfortunately, premature Press publicity necessitated an urgent public announcement in order to allay undue anxiety and to allow of informed Press comment. The Committee regrets that this should have been necessary and apologises to the profession as a whole that things have occurred in this inappropriate order through no fault of its own.
None of the work which has been undertaken would have been possible without the help of a large number of the profession, and the Committee is very grateful for that collaboration. It would, however, urge an increased vigilance on the profession as a whole in relation to adverse reactions from contraceptive medication, and asks that the Committee should be informed at the earliest opportunity of adverse reactions. It is only by this full collaboration that drug-safety problems can be identified and early
warnings given. Queen Anne’s Mansions, Queen Anne’s Gate, London S.W.1.
E. F. SCOWEN Chairman, Committee Safety of Drugs.
on
HEPATIC REACTION TO NITROFURANTOIN SIR,-We have recently seen a woman of 57 who, following 2 weeks’ therapy with nitrofurantoin for chronic pyelonephritis, developed a diffuse pruritic maculopapular rash on both legs, and generalised myalgias and arthralgias. These were associated with absolute eosinophilia (1014 eosinophils per c.mm.), a normal total-serum-bilirubin of 0-5 mg. per 100 ml. (direct van den Bergh reaction negative), 4. 5.
Smith, W. G. Lancet, 1968, ii, 397. Crampton, R. S. J. Am. med. Ass. 1968, 205,
803.
withdrawn and the reaction subsided. Clinical and biochemical features returned to normal within 7 days, except that the E.s.R. remained raised at 47 mm. per hour. In view of the clinical improvement and the emotional instability of the patient, it was not considered justifiable to repeat the liver biopsy. This experience prompted us to survey published reports during the past decade (1960-69) on nitrofurantoin toxicity, with special reference to hepatic complications. We found eighty-four references on the subject. Over 50% of the reported complications were related to the lungs (pneumonias, pulmonary infiltrations, &c.) and peripheral nerves (polyneuritis). The remainder included anaphylaxis, megaloblastic and haemolytic anxmias, skin lesions, eosinophilia, dental disorders, and cardiac arrhythmias. Only six cases 1-6 of non-haemolytic jaundice were discovered, the first having been reported by Ernaelsteen and Williams in 1961.1 In four 1-4 of these there was evidence of intrahepatic cholestasis; in onethe liver-function tests were abnormal and toxic hepatitis was suspected, but liver biopsy was not done because,of a hxmorrhagic diathesis. In the sixth case6 a liver biopsy specimen and liver-function tests were normal, despite a raised serum-bilirubin. Five out of six of these cases of liver involvement were associated with jaundice. Since our patient had clinical and biochemical evidence of liver involvement without jaundice, it seemed worthwhile reporting this case briefly. Department of Pathology and Division of Gastroenterology, St. Michael’s Hospital, ARVIND G. BHAGWAT University of Toronto, RALPH E. WARREN. Toronto, Ontario. EXPERT WITNESSES Dr. RAYMOND GREENE writes: " In the course of my recovery from a painful illness I have examined descriptions of the symptoms in a number of standard textbooks. All of them were completely inadequate. It occurred to me that a book consisting of descriptions of diseases, written by doctors who have suffered from them, might be of value. Heinemann Medical Books Ltd. propose to publish such a book if sufficient material is available. I should be glad if any of your readers who have had a disorder which might be of interest would write a detailed description of the illness and the effects of treatment, and send the manuscript to me c/o William Heinemann Medical Books Ltd., 23 Bedford Square, London W.C.1." HELP FOR BIAFRAN CHILDREN Dr. WENDY SAVAGE writes: " I should like to appeal through your columns for help for the Centre Medicale, Leconi, Republic of Gabon. This centre has been set up, with the aid of the Gabonese Government, primarily to treat Biafran children (this occasionally includes their mothers as well). The Biafran doctor in charge, Onyemara (Dick) Onyeaso, is asking for assistance: he needs money to buy drugs (paediatric sedatives, antibiotics, and vita-
mins)
and equipment (especially extractor, and I.U.C.D.S).
vacuum
an
E.M.O.
machine,
a
I worked with Dr.
1. Ernaelsteen, D., Williams, R. Gastroenterology, 1961, 41, 590. 2. Cook, G. C., Sherlock, S. Lancet, 1965, i, 175. 3. Jokela, S. Gastroenterology, 1967, 53, 306. 4. Wasowska, T., Krus, S. Pol. med. J. 1968, 7, 322. 5. Murphy, K. J., Innis, M. D. J. Am. med. Ass. 1968, 204, 396. 6. Jowers, L. V., Shannon, S. R. Jl. S. Carol. med. Ass. 1967, 63, 357.