- Email: [email protected]
INACTIVE INGREDIENTS IN MEDICINES
224
DRUG PROMOTION IN THE THIRD WORLD
SIR,-Drug companies still exploit the Third World. The manufacturers of ketoconazole, a broad-spectrum antifungal agent, are campaigning in Saudi Arabia for this drug to be taken orally for benign superficial skin conditions. A recent presentation to promote the drug stated that it was the recommended treatment for conditions such as vaginal candidosis, tinea corporis, tinea ungium, and pityriasis versicolor. It is well established, and acknowledged by the manufacturers, that this drug suppresses testosterone production and affects the liver, in some instances fatally. To recommend its prescription for conditions which respond to the proper local treatment is unjustifiable. Ketoconazole (’Nizoral’) is actually marketed as a preparation for local application as well as a systemic drug. The only indications for systemic use in superficial fungus infections are where immunocompromised patients are at risk of a disseminated candidosis. It is especially reprehensible that a campaign for this drug to be prescribed orally for pityriasis versicolor should be pursued in Third World countries, where this condition is common. The basis of treating this disease is to identify the areas of skin affected by ultraviolet light, which demonstrates to the patient the areas of the skin involved. Without this, all suspect areas should be treated. The lesions respond rapidly to various treatments but frequently leave areas of hypo pigmentation. These do not require further antifungal treatment but may be cosmetically worrying although they gradually become normal. To suggest, as is being done, that oral treatment with ketoconazole may have a beneficial effect on this cosmetic
problem has no justification. Pityriasis versicolor is a benign, non-contagious condition, which should be treated locally. There is no place for oral administration of antifungal drugs. Whether liver function tests are normal has no bearing on the method of treatment, which should not vary between countries. Third World countries cannot adequately monitor side-effects, which is important when a new drug is being used. 10 years ago, a similar problem with analgesics occurred in the Gulf states. On that occasion, two company representatives came to interview me. After listening to their arguments for continuing the use of the analgesics, I asked them if they would give them to their own children: they accepted my point. Perhaps all drug companies should use a similar yardstick instead of exploiting the legal system relating to drugs in developing countries. Khalid Hospital, PO Box 9515, Jeddah-21423, Saudi Arabia
King
1. Smith EL.
Pyrazole derivatives
ERIC L. SMITH in
developing countries. Lancet 1978; ii
1312.
INACTIVE INGREDIENTS IN MEDICINES
SiR,—The DHSS proposals for full disclosure of all ingredients (May 21, p 1143) are long overdue. Adverse reactions to excipients have been reported for at least 40 years1 and have included fatalities and near-fatalities as well as lesser morbidity.2 As with adverse reactions to active ingredients, which are known to be under-reported, reports of adverse reactions to "inactive" ingredients must represent only a fraction of the total. At least some of this morbidity could be prevented by disclosure, especially when patients already know of sensitivity to the substances concerned. However, whether the new regulations have the desired effect will depend on how the proposals are implemented. My survey3 of people with unusual sensitivites suggested that one context in which full disclosure could contribute to preventing adverse reactions is during outpatient investigations. Several respondents reported the need for treatment of the adverse effects of substances to which they were exposed during investigation, having tried unsuccessfully to in medicines
ascertain from staff before exposure what these materials contained. The substances included electrode paste and the "fatty meal" mixture used in ’Biloptin’ cholecystograms, which contains egg. At least one of the respondents who reacted adversely knew herself to be sensitive to egg. Though they are not commonly classified as medicines, these materials need to be included in provisions for disclosure.
One difficulty in implementing the proposals is the volume of information involved. In the USA, about 760 substances are approved by the Food and Drug Administration as inactive ingredients in pharmaceuticals.4 Comparable data about excipients permitted in Britain are harder to come by, but no doubt the number is in the hundreds. There will be a need for a consumeroriented guide. Prescribers will also find such a manual useful. Institute of Psychiatry, Denmark Hill, London SE5 8AF
VICKY RIPPERE
Randolph TG. Allergy to so-called ’inert ingredients’ (excipients) of pharmaceutical preparations. Ann Allergy 1950; 8: 519-29. 2. Rippere V. Drug safety and the CSM. J R Soc Med 1988; 81: 184. 3. Rippere V. Social and psychological hazards of environmental intolerance. In: Rees AR, Purcell HJ, eds. Disease and the environment. Chichester: John Wiley & Sons, 1.
1982: 137-45.
JL. Incomplete labeling of pharmaceuticals: N Engl J Med 1983; 309: 439-41.
4. Brown
a
list of ’inactive’
ingredients.
LITIGATION AND PRIVATE PRACTICE
SiR,—Boughton presented a graph projecting that by 1993 doctors in the UK would be facing medical defence subscriptions of /J3089 per annum, a figure that seemed preposterous at the time. However, subscriptions of C4000 or more now seem certain. This exponential rise cannot be accounted for by inflation. The rate of claims against health authorities has increased over the past two decades,2but this by itself is insufficient to account for the 100-fold increase in subscriptions from 1972 to 1987. However, anecdotal evidence suggests that the private sector produces more litigation than the National Health Service in proportion to its relative size. In Scotland, where there is significantly less private practice, medical defence subscriptions are lower than they are in the rest of Britain. There has been a remarkably close correlation over the past ten years between defence union subscriptions and levels of private medical coverage. The correlation (figure) does not imply a causal relationship, but the medical defence organisations have been unable or unwilling to provide a breakdown on levels of settlements in the public (NHS) and the private sectors. Even if relative levels of litigation within the NHS and private sector are not yet a significant issue they will become so as the private sector expands in the UK. Who should bear the costs of soaring indemnity premiums, which cover both NHS and private work? The burden is spread over everyone-junior doctors, academic clinicians, and doctors of all grades who work solely within the NHS. A proposal that the health authorities should pay a proportion of the premiums3 is only a temporary measure. The British Medical Association’s view has been that pay rises should take account of the premiums. This, however, is untenable, both for the reasons outlined in the Review Body’s report3 and also because it means that the NHS is subsidising litigation incurred within the private sector. The fair solution is for health authorities to provide indemnity for all work within the NHS and for reasonable related work (eg,
organisation annual subscriptions and total premiums paid for private medical insurance cover 1968-86.
Medical defence
BUPA = British United Provident Association; PPP= Private Patients Plan; WPA = Western Provident Association.
DRUG PROMOTION IN THE THIRD WORLD
SIR,-Drug companies still exploit the Third World. The manufacturers of ketoconazole, a broad-spectrum antifungal agent, are campaigning in Saudi Arabia for this drug to be taken orally for benign superficial skin conditions. A recent presentation to promote the drug stated that it was the recommended treatment for conditions such as vaginal candidosis, tinea corporis, tinea ungium, and pityriasis versicolor. It is well established, and acknowledged by the manufacturers, that this drug suppresses testosterone production and affects the liver, in some instances fatally. To recommend its prescription for conditions which respond to the proper local treatment is unjustifiable. Ketoconazole (’Nizoral’) is actually marketed as a preparation for local application as well as a systemic drug. The only indications for systemic use in superficial fungus infections are where immunocompromised patients are at risk of a disseminated candidosis. It is especially reprehensible that a campaign for this drug to be prescribed orally for pityriasis versicolor should be pursued in Third World countries, where this condition is common. The basis of treating this disease is to identify the areas of skin affected by ultraviolet light, which demonstrates to the patient the areas of the skin involved. Without this, all suspect areas should be treated. The lesions respond rapidly to various treatments but frequently leave areas of hypo pigmentation. These do not require further antifungal treatment but may be cosmetically worrying although they gradually become normal. To suggest, as is being done, that oral treatment with ketoconazole may have a beneficial effect on this cosmetic
problem has no justification. Pityriasis versicolor is a benign, non-contagious condition, which should be treated locally. There is no place for oral administration of antifungal drugs. Whether liver function tests are normal has no bearing on the method of treatment, which should not vary between countries. Third World countries cannot adequately monitor side-effects, which is important when a new drug is being used. 10 years ago, a similar problem with analgesics occurred in the Gulf states. On that occasion, two company representatives came to interview me. After listening to their arguments for continuing the use of the analgesics, I asked them if they would give them to their own children: they accepted my point. Perhaps all drug companies should use a similar yardstick instead of exploiting the legal system relating to drugs in developing countries. Khalid Hospital, PO Box 9515, Jeddah-21423, Saudi Arabia
King
1. Smith EL.
Pyrazole derivatives
ERIC L. SMITH in
developing countries. Lancet 1978; ii
1312.
INACTIVE INGREDIENTS IN MEDICINES
SiR,—The DHSS proposals for full disclosure of all ingredients (May 21, p 1143) are long overdue. Adverse reactions to excipients have been reported for at least 40 years1 and have included fatalities and near-fatalities as well as lesser morbidity.2 As with adverse reactions to active ingredients, which are known to be under-reported, reports of adverse reactions to "inactive" ingredients must represent only a fraction of the total. At least some of this morbidity could be prevented by disclosure, especially when patients already know of sensitivity to the substances concerned. However, whether the new regulations have the desired effect will depend on how the proposals are implemented. My survey3 of people with unusual sensitivites suggested that one context in which full disclosure could contribute to preventing adverse reactions is during outpatient investigations. Several respondents reported the need for treatment of the adverse effects of substances to which they were exposed during investigation, having tried unsuccessfully to in medicines
ascertain from staff before exposure what these materials contained. The substances included electrode paste and the "fatty meal" mixture used in ’Biloptin’ cholecystograms, which contains egg. At least one of the respondents who reacted adversely knew herself to be sensitive to egg. Though they are not commonly classified as medicines, these materials need to be included in provisions for disclosure.
One difficulty in implementing the proposals is the volume of information involved. In the USA, about 760 substances are approved by the Food and Drug Administration as inactive ingredients in pharmaceuticals.4 Comparable data about excipients permitted in Britain are harder to come by, but no doubt the number is in the hundreds. There will be a need for a consumeroriented guide. Prescribers will also find such a manual useful. Institute of Psychiatry, Denmark Hill, London SE5 8AF
VICKY RIPPERE
Randolph TG. Allergy to so-called ’inert ingredients’ (excipients) of pharmaceutical preparations. Ann Allergy 1950; 8: 519-29. 2. Rippere V. Drug safety and the CSM. J R Soc Med 1988; 81: 184. 3. Rippere V. Social and psychological hazards of environmental intolerance. In: Rees AR, Purcell HJ, eds. Disease and the environment. Chichester: John Wiley & Sons, 1.
1982: 137-45.
JL. Incomplete labeling of pharmaceuticals: N Engl J Med 1983; 309: 439-41.
4. Brown
a
list of ’inactive’
ingredients.
LITIGATION AND PRIVATE PRACTICE
SiR,—Boughton presented a graph projecting that by 1993 doctors in the UK would be facing medical defence subscriptions of /J3089 per annum, a figure that seemed preposterous at the time. However, subscriptions of C4000 or more now seem certain. This exponential rise cannot be accounted for by inflation. The rate of claims against health authorities has increased over the past two decades,2but this by itself is insufficient to account for the 100-fold increase in subscriptions from 1972 to 1987. However, anecdotal evidence suggests that the private sector produces more litigation than the National Health Service in proportion to its relative size. In Scotland, where there is significantly less private practice, medical defence subscriptions are lower than they are in the rest of Britain. There has been a remarkably close correlation over the past ten years between defence union subscriptions and levels of private medical coverage. The correlation (figure) does not imply a causal relationship, but the medical defence organisations have been unable or unwilling to provide a breakdown on levels of settlements in the public (NHS) and the private sectors. Even if relative levels of litigation within the NHS and private sector are not yet a significant issue they will become so as the private sector expands in the UK. Who should bear the costs of soaring indemnity premiums, which cover both NHS and private work? The burden is spread over everyone-junior doctors, academic clinicians, and doctors of all grades who work solely within the NHS. A proposal that the health authorities should pay a proportion of the premiums3 is only a temporary measure. The British Medical Association’s view has been that pay rises should take account of the premiums. This, however, is untenable, both for the reasons outlined in the Review Body’s report3 and also because it means that the NHS is subsidising litigation incurred within the private sector. The fair solution is for health authorities to provide indemnity for all work within the NHS and for reasonable related work (eg,
organisation annual subscriptions and total premiums paid for private medical insurance cover 1968-86.
Medical defence
BUPA = British United Provident Association; PPP= Private Patients Plan; WPA = Western Provident Association.