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Eur J Clin Pharmacol. 2007 Apr;63(4):409-15. Epub 2007 Feb 16.

Use and safety profile of antiepileptic drugs in Italy.

Iorio ML, Moretti U, Colcera S, Magro L, Meneghelli I, Motola D, Rivolta AL, Salvo F, Velo GP.

Source

Clinical Pharmacology Unit, Reference Centre for Education and Communication within the WHO Programme for International Drug Monitoring, University of Verona, Verona, Italy.

Abstract

OBJECTIVE:

To analyse and discuss the use and the safety profile of individual antiepileptic drugs (AEDs) in Italy.

METHODS:

The AED safety data referred to the period January 1988-June 2005 and were obtained from the database of the Italian Interregional Group of Pharmacovigilance (GIF).

This database collects all spontaneous reports of suspected adverse drug reactions (ADRs) from six Italian regions which are the main contributors to the Italian spontaneous reporting system.

Individual AED consumption data (defined daily dose/1,000 inhabitants per day) in the GIF area and in the whole of Italy referred to the period January 2003-June 2005 and were derived from drug sales data (Institute for Medical Statistics Health).

RESULTS:

Phenobarbital was the most frequently used AED in the GIF area (4.26 DDD/1,000 inhabitants per day) followed by carbamazepine (1.97), valproic acid (1.33) and gabapentin (1.10). AED consumption in the whole of Italy showed a similar pattern.

Gabapentin was the most frequently used AED among newer AEDs. In the GIF database 37,906 reports (up to June 2005) were present; 666 of them (1.76%) were associated with at least one AED (Anatomical Therapeutic Chemical code N03A).

The AED with the highest number of reports was carbamazepine (208 reports) followed by phenobarbital (98), gabapentin (80), phenytoin (56), valproic acid (55), lamotrigine (51), oxcarbazepine (43) and vigabatrin (35). Use and toxicity profile were evaluated only for AEDs associated with at least 30 reports.

Skin reactions were the most frequently reported ADRs, followed by haematological, general condition, hepatic, neurological and gastrointestinal adverse reactions.

Phenobarbital, lamotrigine, carbamazepine and phenytoin had the highest percentage of skin reactions (69, 67, 60 and 54%, respectively). Many haematological reactions were reported for each AED; the highest percentage was related to valproic acid (25%). V

igabatrin was associated with the highest percentage of reactions related to hearing, vision and other senses (97%). Phenytoin and valproic acid had the highest percentage of hepatic reactions (30 and 20%), whereas gabapentin of nervous system, psychiatric, gastrointestinal and urinary reactions (26, 21, 21 and 14%, respectively) and phenobarbital of musculoskeletal reactions (13%).

CONCLUSIONS:

In Italy antiepileptic drug therapy appears to be still dominated by traditional drugs. Our analysis showed a different safety profile related to each AED.

Some of the drug-adverse reaction associations discussed are not included in the Italian drug leaflets or have not been reported before in the literature.

PMID:
17347806
[PubMed - indexed for MEDLINE]

 

Neurology. 2005 Apr 12;64(7):1134-8.

Risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptics.

Mockenhaupt M, Messenheimer J, Tennis P, Schlingmann J.

Source

University of Freiburg, Freiburg, Germany.

Abstract

BACKGROUND:

Estimates of risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) associated with some antiepileptic drugs (AEDs) have used denominators based on the number of prescriptions or daily doses.

Because the risk of SJS is highest in new users of drugs, the use of denominators reflective of all users can lead to low estimates of risk associated with drugs. In this study, risk in new users is assessed.

METHODS:

Data on all hospitalized patients with SJS and TEN with use of carbamazepine (CBZ), lamotrigine (LTG), phenobarbital (PHB), phenytoin (PHT), or valproic acid (VPA) were obtained from the German Registry for Serious Cutaneous Reactions.

For 1998-2001, the numbers of new users were estimated from number of dispensed prescriptions in Germany, the average prescribed doses, and the duration of use in the Mediplus database (IMS Health) Germany, and assumptions that relate new use to growth in national dispensings. To minimize the probability of underestimating risk in new users, conservative estimates of new use that were somewhat lower than predicted from national prescription data were used.

RESULTS:

More than 90% of SJS and TEN cases occurred in the first 63 days of AED use.

Over the 4 years, increases in dispensing were 5% for CBZ, 65% for LTG, 6% for PHB, -16% for PHT, and 26% for VPA.

Across a range of assumptions about frequency of incident use, the risk estimates vary between 1 and 10 per 10,000 new users for CBZ, LTG, PHT, and PHY and were consistently lower for VPA.

CONCLUSION:

Across a range of assumptions used, the risk of hospitalization for Stevens-Johnson syndrome or toxic epidermal necrolysis in new users is low for carbamazepine, lamotrigine, phenytoin, phenobarbital, and valproic acid.

Because conservative incidence use fractions were used, it is likely that some risks were overestimated.

PMID:
15824335
[PubMed - indexed for MEDLINE]

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http://rarediseases.info.nih.gov/GARD/Condition
/7700/StevensJohnson_syndrome.aspx

Stevens-Johnson syndrome
ORDR lists rare diseases for information purposes only and does not guarantee that a condition is rare. Read more
 The links on this page may take you to sites outside of the NIH. (See for details.)

Stevens-Johnson Syndrome (SJS), also called erythema multiforme major, is a limited form of toxic epidermal necrolysis. This disorder affects the skin, mucous membranes and eyes.[1][2] Stevens-Johnson syndrome occurs twice as often in men as women, and most cases appear in children and young adults under 30, although it can develop in people at any age.[1] It is an emergency medical condition that usually requires hospitalization. Treatment focuses on eliminating the underlying cause, controlling symptoms and minimizing complications.[3]


References

Facts About The Cornea and Corneal Disease. National Eye Institute (NEI). 2010 Available at: http://www.nei.nih.gov/health/cornealdisease/#m. Accessed March 15, 2010.

Roujeau JC. Stevens-Johnson syndrome. Orphanet. 2009 Available at: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=36426. Accessed March 15, 2010.

Stevens-Johnson syndrome. MayoClinic.com. 2009 Available at: http://www.mayoclinic.com/health/stevens-johnson-syndrome/DS00940/METHOD=print. Accessed March 15, 2010.


Questions & Answers (Found 1 Question)
A list of questions from the public on rare and/or genetic diseases that have been answered by the Genetic and Rare Disease Information Center. Click on each question to find the answer.

More Detailed Information (Found 8 resources)
Links where you can find more general information, comprehensive resources, selected full text journal articles, and news updates

  • General

    • MedlinePlus, a Web site designed by the National Library of Medicine Web site to help you research your health questions, provides more information about this topic. Click on the link to view this information.
    • The Merck Manuals Online Medical Library provides information on this condition. Click on the link to view the information.
    • The National Eye Institute (NEI) was established by Congress in 1968 to protect and prolong the vision of the American people. Click on the link to view information on this topic
    • .
    • The Online Mendelian Inheritance in Man (OMIM) database contains genetics resources that discuss Stevens-Johnson syndrome. Click on the link to go to OMIM and review these resources.
    • Orphanet is a database dedicated to information on rare diseases and orphan drugs. Access to this database is free of charge. Click on the link to read information on this topic.
    • PubMed is a searchable database of medical literature and lists journal articles that discuss Stevens-Johnson syndrome. Click on the link to view a sample search on this topic.
    • eMedicine has 4 articles on this topic from the perspective of Emergency Medicine, Infectious Diseases, Ophthalmology and Dermatology.
    • You may need to register to view the information online, but registration is free. Click on the links above to view the articles from this medical reference Web site.
    • The MayoClinic.com web site provides information about Stevens-Johnson syndrome. Click on the link to view this information.

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Drug Saf. 2000 Dec;23(6):483-507.

Immunological principles of adverse drug reactions: the initiation and propagation of immune responses elicited by drug treatment.

Naisbitt DJ, Gordon SF, Pirmohamed M, Park BK.

Source

Department of Pharmacology and Therapeutics, University of Liverpool, Merseyside, England. dnes@liv.ac.uk

Abstract

Adverse drug reactions account for between 2 to 5% of all hospital admissions and can prevent the administration of an otherwise effective therapeutic agent.

Hypersensitivity or immune-mediated reactions, although less common, tend to be proportionately more serious. There is convincing evidence to implicate the immune system in the pathogenesis of hypersensitivity reactions.

Our understanding of the way in which the immune system recognises drugs is based on the hapten hypothesis; the onset of hypersensitivity involves drug bioactivation, covalent binding to proteins, followed by uptake, antigen processing and T cell proliferation. Central to this hypothesis is the critical role of drug metabolism, with the balance between metabolic bioactivation and detoxification being one important component of individual susceptibility.

The purpose of this review is to classify drug hypersensitivity reactions in terms of their clinical presentation, and also to consider recent advances in our understanding of the chemical, biochemical and, in particular, cellular immunological mechanisms of hypersensitivity.

The following topics are reviewed: (i) drug disposition and cellular metabolism; (ii) mechanisms of antigen processing and presentation; (iii) the role of cytokines and co-stimulatory molecules in the induction and maintenance of a polarised immune response; and (iv) the application of the hapten hypothesis, danger hypothesis and serial triggering model to drug hypersensitivity.

A greater understanding of the mechanism(s) of hypersensitivity may identify novel therapeutic strategies and help to combat one of the more severe forms of adverse reactions to drugs.