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Global warming and performance of antiepileptic therapeutics
Seizure 1999; 8: 195–196
Article No. seiz.1998.0269, available online at http://www.idealibrary.com on
CORRESPONDENCE
Global warming and performance of antiepileptic therapeutics Dear Sir, During early 1990s, there were 30 million patients with epilepsy in the world1 . They require long-term medication with various antiepiletic formulations. The efficacy of various therapeutic formulations being offered to those suffering from an epileptic disorder (Table 1) could be severely lowered in the face of impending global warming and frequent occurrence of the El ni˜no effects. Even though the recommended storage temperatures for various antiepileptics (Table 1) range between 15–25 ◦ C or 15–30 ◦ C2 , and none requires refrigeration facilities, an inadvertent exposure to higher temperatures could vitiate their therapeutic efficacy. A new record concerning global temperatures was established during July 1998, when the average global temperature reached 15.5 ◦ C, and July 1998 was recorded as the hottest month in nearly 120 years3 . Moreover, high ambient temperatures when accompanied by high humidity would involve enormous transmission of heat to antiepileptics. This was evident during the 1995 heatwave in Chicago when the maximum temperature recorded was 40 ◦ C, though the heatindex, the estimate of radiative and evaporative transfer of heat, was 48.3 ◦ C4 . The high heat-index in developing countries when accompanied by poor electricity supplies would upset electrically-operated cooling facilities5 . The cumulative effect of high ambient temperatures, heat-index and poor air-cooling would be disastrous on potency and bioavailability of various antiepileptics. The antiepileptic formulations (Table 1) with desired storage temperature maxima of 25 or 30 ◦ C2 , would not be expected to behave differently from therapeutic agents with identical storage requirements during field usage. This is vindicated from the field efficacy of ampicillin, sulfamethoxazole and trimethoprim, storage temperature not exceeding 25 ◦ C2 , and acetaminophen and vitamin B2 preparations, storage temperature not exceeding 30 ◦ C2 , in Bangladesh during the early 1990s. An analysis of 137 brands of the above four therapeutics, being marketed in various regions of Bangladesh, for residual potency, revealed that there were 37 sub-standard formulations being offered 1059–1311/99/030195 + 02
$12.00/0
to the public. Of the 16 brands of acetaminophen and 10 brands of ampicillin that were found to be sub-standard during the analysis, 11 and eight brands, respectively, had already been assessed as sub-standard by the regulatory authorities6 .
Table 1: Recommended temperatures for storage of anti-convulsant agents. 15–25 ◦ C Controlled temperature of 15 ◦ C–30 ◦ C (or 30 ◦ C) Benzodiazepines Barbiturates • diazepam • phenobarbitonea • clorazepate Benzodiazepines • nitrazepam • clonazepam Phenyltriazine Hydantoins • Lamotrigine • ethylphenylhydantoin Oxazolidinediones • phenytoin • Trimethadone GABA analogues Miscellaneous • gabapentin, vigabatrin • Sodium valproate Dicarbamate • primidone • Felbamate Succinimides • Ethosaximide • Methsuximide Around 15 ◦ C Sulphamate • Topiramate • Paraldehyde Miscellaneous • Carbamazepine a And others.
The inimical effects of high temperature and heatindex3, 4 on various antiepileptics (Table 1) should be tackled by stabilization against adverse environmental changes. Efforts have been directed to stabilize live vaccines by incorporation of trehalose, deuterium oxide, pirodavir, or compounds based on electrostatic intervention7 . Furthermore, it would be desirable to insist on distinctive marks on antiepileptic formulation tablets, vials or capsules, to indicate the desired temperature for storage. Similar symbols have been mandatory for inflammables, poisons and radioactive substances. Well stabilized therapeutic agents directed against different convulsive disorders (Table 1) would ensure maintenance of potency and bioavailability in the face of adverse global environmental change. This would eliminate any failures or sub-optimal response to otherwise efficient antiepileptic agents in clinical practice. c 1999 BEA Trading Ltd
196
References 1. }WHO. The World Health Report 1995: Bridging the Gaps. Geneva, WHO, 1995. p. 34. 2. }Physicians’ Desk Reference. 51st Edition. Montvale, Medical Economics Company, 1997. 3. }United States Environmental Protection Agency. Global Warming. Vice President Gore announces new data showing July 1998 was the hottest month on record. 1998. 4. }Heat-related mortality Chicago, July 1995. MMWR 1995; 44: 577–579. 5. }Kumar, S. India’s heat wave and rains result in massive death toll. Lancet 1998; 351: 1869.
6. }Roy, J. The menance of substandard drugs. World Health Forum 1994; 15: 406–407. 7. }New Approaches to Stabilisation of Vaccine Potency. (Ed. F. Brown) Karger, Basel, 1996.
SUBHASH C. ARYA Centre for Logistical Research and Innovation, M-122 (of part 2), Greater Kailash-II, New Delhi- 110048, India
Article No. seiz.1998.0269, available online at http://www.idealibrary.com on
CORRESPONDENCE
Global warming and performance of antiepileptic therapeutics Dear Sir, During early 1990s, there were 30 million patients with epilepsy in the world1 . They require long-term medication with various antiepiletic formulations. The efficacy of various therapeutic formulations being offered to those suffering from an epileptic disorder (Table 1) could be severely lowered in the face of impending global warming and frequent occurrence of the El ni˜no effects. Even though the recommended storage temperatures for various antiepileptics (Table 1) range between 15–25 ◦ C or 15–30 ◦ C2 , and none requires refrigeration facilities, an inadvertent exposure to higher temperatures could vitiate their therapeutic efficacy. A new record concerning global temperatures was established during July 1998, when the average global temperature reached 15.5 ◦ C, and July 1998 was recorded as the hottest month in nearly 120 years3 . Moreover, high ambient temperatures when accompanied by high humidity would involve enormous transmission of heat to antiepileptics. This was evident during the 1995 heatwave in Chicago when the maximum temperature recorded was 40 ◦ C, though the heatindex, the estimate of radiative and evaporative transfer of heat, was 48.3 ◦ C4 . The high heat-index in developing countries when accompanied by poor electricity supplies would upset electrically-operated cooling facilities5 . The cumulative effect of high ambient temperatures, heat-index and poor air-cooling would be disastrous on potency and bioavailability of various antiepileptics. The antiepileptic formulations (Table 1) with desired storage temperature maxima of 25 or 30 ◦ C2 , would not be expected to behave differently from therapeutic agents with identical storage requirements during field usage. This is vindicated from the field efficacy of ampicillin, sulfamethoxazole and trimethoprim, storage temperature not exceeding 25 ◦ C2 , and acetaminophen and vitamin B2 preparations, storage temperature not exceeding 30 ◦ C2 , in Bangladesh during the early 1990s. An analysis of 137 brands of the above four therapeutics, being marketed in various regions of Bangladesh, for residual potency, revealed that there were 37 sub-standard formulations being offered 1059–1311/99/030195 + 02
$12.00/0
to the public. Of the 16 brands of acetaminophen and 10 brands of ampicillin that were found to be sub-standard during the analysis, 11 and eight brands, respectively, had already been assessed as sub-standard by the regulatory authorities6 .
Table 1: Recommended temperatures for storage of anti-convulsant agents. 15–25 ◦ C Controlled temperature of 15 ◦ C–30 ◦ C (or 30 ◦ C) Benzodiazepines Barbiturates • diazepam • phenobarbitonea • clorazepate Benzodiazepines • nitrazepam • clonazepam Phenyltriazine Hydantoins • Lamotrigine • ethylphenylhydantoin Oxazolidinediones • phenytoin • Trimethadone GABA analogues Miscellaneous • gabapentin, vigabatrin • Sodium valproate Dicarbamate • primidone • Felbamate Succinimides • Ethosaximide • Methsuximide Around 15 ◦ C Sulphamate • Topiramate • Paraldehyde Miscellaneous • Carbamazepine a And others.
The inimical effects of high temperature and heatindex3, 4 on various antiepileptics (Table 1) should be tackled by stabilization against adverse environmental changes. Efforts have been directed to stabilize live vaccines by incorporation of trehalose, deuterium oxide, pirodavir, or compounds based on electrostatic intervention7 . Furthermore, it would be desirable to insist on distinctive marks on antiepileptic formulation tablets, vials or capsules, to indicate the desired temperature for storage. Similar symbols have been mandatory for inflammables, poisons and radioactive substances. Well stabilized therapeutic agents directed against different convulsive disorders (Table 1) would ensure maintenance of potency and bioavailability in the face of adverse global environmental change. This would eliminate any failures or sub-optimal response to otherwise efficient antiepileptic agents in clinical practice. c 1999 BEA Trading Ltd
196
References 1. }WHO. The World Health Report 1995: Bridging the Gaps. Geneva, WHO, 1995. p. 34. 2. }Physicians’ Desk Reference. 51st Edition. Montvale, Medical Economics Company, 1997. 3. }United States Environmental Protection Agency. Global Warming. Vice President Gore announces new data showing July 1998 was the hottest month on record. 1998. 4. }Heat-related mortality Chicago, July 1995. MMWR 1995; 44: 577–579. 5. }Kumar, S. India’s heat wave and rains result in massive death toll. Lancet 1998; 351: 1869.
6. }Roy, J. The menance of substandard drugs. World Health Forum 1994; 15: 406–407. 7. }New Approaches to Stabilisation of Vaccine Potency. (Ed. F. Brown) Karger, Basel, 1996.
SUBHASH C. ARYA Centre for Logistical Research and Innovation, M-122 (of part 2), Greater Kailash-II, New Delhi- 110048, India