- Email: [email protected]
Warning on cyproterone
made up of
need "extra protection" (eg, be allowed to force the patient to undergo treatment) before making such a decision, was expressed eloquently during the disciplinary college’s 9-hour final session last week by R J van den Hoofdakker, professor of biological psychiatry at the University of Groningen. A psychiatrist and psychotherapist who specialises in severe depression, he is also a poet writing under the pseudonym Rutger Kopland. He was a case had increased rather than undermined the public’s trust in the medical witness called by the college. He also expressed his views in last Saturday’s profession. Chabot told the panel that the woman’s evening newspaper NRC Handelsblad, depression following a complicated when he wrote about the boundaries of the power of doctors. "This power has mourning process was an adaptation reaction to an irreparable catastrophic or tragbeen given to us doctors, together with ic situation. There was much controversy the key to the medicine cupboard, and it over the diagnosis of depression. In addiis a heavy burden", he wrote. He concludtion, the evidence collected by the panel ed that, although Chabot had done his was that most cases of severe depression very best for the patient, he went across do respond to psychological and pharmathe border. The Dutch public will know cological treatment. Chabot’s patient had within the next 2 months whether the dispersistently refused treatment. The third ciplinary college agrees with van den point-that the patient ought to be seen Hoofdakker. The case might not end here. An appeal by more than one doctor-had already: been accepted and addressed by the to the Central Disciplinary College in the Supreme Court. : Hague is possible. The reservation about whether assisted suicide is the right way of relieving severe mental suffering, and whether doctors Marjanke Spanjer two lawyers (one the psychiatrist, one neurologist, one anaesthetist, and one general practitioner. Mr E Sutorius, Chabot’s defence lawyer, pointed out that the disciplinary college had very narrow margins within which to make a judgment since the Supreme Court had already found Chabot guilty but had decided not to impose a penalty. He also asserted that the was
chairman),
one
1
1
warning (Lancet 1994; 344: 602) because of suspected genotoxicity. The CPMP noted that cyproterone-associated primary hepatic cancer (Lancet 1994; 344: 1567-69) is uncommon. Nevertheless, it recommends that product information for all cyproterone acetate preparations carry a statement saying: "Recognised first-line tests of genotoxicity gave negative results
Warning on cyproterone
The European Union Committee for ProProducts Medicinal has prietary recommended that product information for medicines containing 50 mg or more of cyproterone acetate (CPA) should carry a standard hepatotoxicity warning. The CPMP hepatotoxicity statement says: : "Direct hepatic toxicity ... has been when conducted with CPA. However, furreported in patients treated with 200-300 ther tests showed that CPA was capable of adducts with DNA and an mg cyproterone acetate. Most reported producing increase in DNA-repair activity in liver cases are in men with prostatic cancer. from rats and monkeys and also in cells Toxicity is dose-related and develops, usually, several months after treatment has1 freshly isolated human hepatocytes. This begun". The statement adds that when DNA-adduct formation occurred at expoliver function tests suggest hepatotoxicity, . sures that might be expected to occur in the drug should normally be withdrawn, the recommended dose regimens for CPA. unless the hepatotoxicity is due to another One in vivo consequence of CPA treatment was the increased incidence of focal, cause (eg, metastatic disease) in which liver lesions in case the drug should be continued only if possibly pre-neoplastic, 1 which were altered in cellular enzymes the perceived benefit outweighs the risk. : The CPMP launched an investigation female rats. "The clinical relevance of these findings into cyproterone acetate at the end of is uncertain. Clinical experience presently after a issued August Germany rapid alert date would not support an increased incidence of hepatic tumours in man". The CPMP opinion also said that cyproterone acetate may continue to be used to treat sexual deviation in adult males at a dosage from 50 mg daily, but the indication of precocious puberty "is to
Droxicam The CPMP has recommended that marketing authorisations for the nonsteroidal anti-inflammatory (NSAID) droxicam be suspended because of risk of hepatic damage. The product is authorised in Spain, Italy, and Belgium. The risk of hepatic damage differs from that shown by other NSAIDs, including piroxicam. Droxicam acts as a prodrug of piroxicam.
: : : : :
no
longer
appropriate".
ment
50 mg and
Cyproterone
may continue to be recommended for use in the manageacetate
over
of patients with
: Sara Lewis
prostatic
cancer
Lowering the US hurdles for AIDS drugs The National Task Force on AIDS Drug Development is to report to the Secretary of Health and Human Services Donna Shalala on policies by which the government can stimulate drug development. Chaired by Assistant Secretary for Health Philip R Lee, the panel includes Commissioner of Food and Drugs David A Kessler, National Institutes of Health director Harold E Varmus, university and drug industry researchers, and various patient advocates. They capped their first year of work on Jan 19 by adopting a list of recommendations aimed at getting more drugs discovered and into production. There was general agreement that : incentives should be explored to encourage industry to stay in the war on AIDS for the long haul; zidovudine is the only drug that has generated substantial revenues to date. Accelerated review was discussed as a means of extending the effective duration of patents, as was extension of exclusivity rights. The president’s proposal to eliminate tax credits for research and development was assailed as a bad idea in this context. A loud controversy erupted over the : fair-pricing clauses in Cooperative Research and Development Agreements (CRADAs). In these, the NIH bears some of the initial costs and risks of drug discovery and phase I and II testing and then assigns licence for the production of the drug to industry. Varmus stated that many companies had been unwilling to be bound by such price-control agreements, and he recommended that the panel adopt a recommendation to review the policy of requiring such clauses in CRADAs. A dozen members of the activist group ACT UP contested this view, and challenged Varmus to name the companies that had declined to participate in drug development for this reason (he did not). The activists maintained that the clause is not a true barrier to drug development, and that it is already poorly enforced. They pointed to the US$600 million profit from zidovudine, which was developed in cooperation with the National Cancer Institute. Having said their piece, the ACT UP members silenced the meeting for several minutes by blowing whistles and chanting "They get richer, we die!", and marched out. The resolution to review the fair-pricing clause was adopted, with 4 dissents and 1 abstention. While recommending that the gene: therapy review requirements imposed by the Food and Drug Administration and NIH be combined into one process, the panel recognised that this is already being done. They also applauded the Patent and Trademark Office’s stated intention to accept in-vitro and surrogate marker evidence of efficacy for the issuance of
247
.
need "extra protection" (eg, be allowed to force the patient to undergo treatment) before making such a decision, was expressed eloquently during the disciplinary college’s 9-hour final session last week by R J van den Hoofdakker, professor of biological psychiatry at the University of Groningen. A psychiatrist and psychotherapist who specialises in severe depression, he is also a poet writing under the pseudonym Rutger Kopland. He was a case had increased rather than undermined the public’s trust in the medical witness called by the college. He also expressed his views in last Saturday’s profession. Chabot told the panel that the woman’s evening newspaper NRC Handelsblad, depression following a complicated when he wrote about the boundaries of the power of doctors. "This power has mourning process was an adaptation reaction to an irreparable catastrophic or tragbeen given to us doctors, together with ic situation. There was much controversy the key to the medicine cupboard, and it over the diagnosis of depression. In addiis a heavy burden", he wrote. He concludtion, the evidence collected by the panel ed that, although Chabot had done his was that most cases of severe depression very best for the patient, he went across do respond to psychological and pharmathe border. The Dutch public will know cological treatment. Chabot’s patient had within the next 2 months whether the dispersistently refused treatment. The third ciplinary college agrees with van den point-that the patient ought to be seen Hoofdakker. The case might not end here. An appeal by more than one doctor-had already: been accepted and addressed by the to the Central Disciplinary College in the Supreme Court. : Hague is possible. The reservation about whether assisted suicide is the right way of relieving severe mental suffering, and whether doctors Marjanke Spanjer two lawyers (one the psychiatrist, one neurologist, one anaesthetist, and one general practitioner. Mr E Sutorius, Chabot’s defence lawyer, pointed out that the disciplinary college had very narrow margins within which to make a judgment since the Supreme Court had already found Chabot guilty but had decided not to impose a penalty. He also asserted that the was
chairman),
one
1
1
warning (Lancet 1994; 344: 602) because of suspected genotoxicity. The CPMP noted that cyproterone-associated primary hepatic cancer (Lancet 1994; 344: 1567-69) is uncommon. Nevertheless, it recommends that product information for all cyproterone acetate preparations carry a statement saying: "Recognised first-line tests of genotoxicity gave negative results
Warning on cyproterone
The European Union Committee for ProProducts Medicinal has prietary recommended that product information for medicines containing 50 mg or more of cyproterone acetate (CPA) should carry a standard hepatotoxicity warning. The CPMP hepatotoxicity statement says: : "Direct hepatic toxicity ... has been when conducted with CPA. However, furreported in patients treated with 200-300 ther tests showed that CPA was capable of adducts with DNA and an mg cyproterone acetate. Most reported producing increase in DNA-repair activity in liver cases are in men with prostatic cancer. from rats and monkeys and also in cells Toxicity is dose-related and develops, usually, several months after treatment has1 freshly isolated human hepatocytes. This begun". The statement adds that when DNA-adduct formation occurred at expoliver function tests suggest hepatotoxicity, . sures that might be expected to occur in the drug should normally be withdrawn, the recommended dose regimens for CPA. unless the hepatotoxicity is due to another One in vivo consequence of CPA treatment was the increased incidence of focal, cause (eg, metastatic disease) in which liver lesions in case the drug should be continued only if possibly pre-neoplastic, 1 which were altered in cellular enzymes the perceived benefit outweighs the risk. : The CPMP launched an investigation female rats. "The clinical relevance of these findings into cyproterone acetate at the end of is uncertain. Clinical experience presently after a issued August Germany rapid alert date would not support an increased incidence of hepatic tumours in man". The CPMP opinion also said that cyproterone acetate may continue to be used to treat sexual deviation in adult males at a dosage from 50 mg daily, but the indication of precocious puberty "is to
Droxicam The CPMP has recommended that marketing authorisations for the nonsteroidal anti-inflammatory (NSAID) droxicam be suspended because of risk of hepatic damage. The product is authorised in Spain, Italy, and Belgium. The risk of hepatic damage differs from that shown by other NSAIDs, including piroxicam. Droxicam acts as a prodrug of piroxicam.
: : : : :
no
longer
appropriate".
ment
50 mg and
Cyproterone
may continue to be recommended for use in the manageacetate
over
of patients with
: Sara Lewis
prostatic
cancer
Lowering the US hurdles for AIDS drugs The National Task Force on AIDS Drug Development is to report to the Secretary of Health and Human Services Donna Shalala on policies by which the government can stimulate drug development. Chaired by Assistant Secretary for Health Philip R Lee, the panel includes Commissioner of Food and Drugs David A Kessler, National Institutes of Health director Harold E Varmus, university and drug industry researchers, and various patient advocates. They capped their first year of work on Jan 19 by adopting a list of recommendations aimed at getting more drugs discovered and into production. There was general agreement that : incentives should be explored to encourage industry to stay in the war on AIDS for the long haul; zidovudine is the only drug that has generated substantial revenues to date. Accelerated review was discussed as a means of extending the effective duration of patents, as was extension of exclusivity rights. The president’s proposal to eliminate tax credits for research and development was assailed as a bad idea in this context. A loud controversy erupted over the : fair-pricing clauses in Cooperative Research and Development Agreements (CRADAs). In these, the NIH bears some of the initial costs and risks of drug discovery and phase I and II testing and then assigns licence for the production of the drug to industry. Varmus stated that many companies had been unwilling to be bound by such price-control agreements, and he recommended that the panel adopt a recommendation to review the policy of requiring such clauses in CRADAs. A dozen members of the activist group ACT UP contested this view, and challenged Varmus to name the companies that had declined to participate in drug development for this reason (he did not). The activists maintained that the clause is not a true barrier to drug development, and that it is already poorly enforced. They pointed to the US$600 million profit from zidovudine, which was developed in cooperation with the National Cancer Institute. Having said their piece, the ACT UP members silenced the meeting for several minutes by blowing whistles and chanting "They get richer, we die!", and marched out. The resolution to review the fair-pricing clause was adopted, with 4 dissents and 1 abstention. While recommending that the gene: therapy review requirements imposed by the Food and Drug Administration and NIH be combined into one process, the panel recognised that this is already being done. They also applauded the Patent and Trademark Office’s stated intention to accept in-vitro and surrogate marker evidence of efficacy for the issuance of
247
.