Lamotrigine and toxic epidermal necrolysis

Sachs, B.; Rönnau, Andrea C.; Ruzicka, Thomas; Gleichmann, Ernst; Schuppe, Hans‐Christian

doi:10.1016/s0140-6736(05)66227-7

Cited by 25 publications

(17 citation statements)

References 4 publications

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“…In addition, there were no immediate response (within 20 min) observed in both the formulations; however, the LTGS induced wheal formation as a result of late hypersensitivity response, while the same was absent for LTG-NPs. This is because of the property of LTG which induces severe rashes and epidermal necrosis through the activation of T lymphocytes; on the other hand, entrapment of LTG inside NPs decreases the exposure of free drugs to the skin and decreases toxicity (6).…”

Section: Intradermal Skin Testmentioning

confidence: 99%

“…Lamotrigine (LTG), a sodium and calcium channel blocker, has demonstrated efficacy for the treatment of neuropathic pain in multiple, randomized, controlled trials (5). However, its potential clinical applications in neuropathic pain are limited due to the risk of dose-dependent severe rashes, as well as Stevens-Johnson syndrome, a potentially fatal epidermal necrosis associated with high dose and rapid dose escalation as a result of ability of LTG to activate T lymphocytes (6). Although LTG has sufficient lipophilicity (log P of 1.87) ensuring a rapid onset of action, it is not retained in the brain for longer time, and a rapid decline in the brain concentration occurs diminishing the analgesic action of drug (7).…”

Section: Introductionmentioning

confidence: 99%

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Protein-Functionalized PLGA Nanoparticles of Lamotrigine for Neuropathic Pain Management

et al. 2014

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Abstract. Lamotrigine (LTG), a sodium and calcium channel blocker, has demonstrated efficacy for the treatment of neuropathic pain in multiple, randomized, controlled trials. However, its potential clinical applications in neuropathic pain are limited due to the risk of dose-dependent severe rashes associated with high dose and prompt dose escalation. Further, the poor pharmacokinetic profile due to non-selective distribution to organs other than brain reduces the efficacy of dosage regimen. Therefore, the aim of present investigation is to develop surface-engineered LTG nanoparticles (NPs) using transferrin and lactoferrin as ligand to deliver higher amount of drug to brain and improve the biodistribution and pharmacokinetic profile of drug with prolonged duration of action and reduced accumulation in nontarget organs. The LTG NPs were prepared by nanoprecipitation and optimized by factorial design for high entrapment and optimized particle size. The optimized NPs were surface functionalized by conjugating with the lactoferrin (Lf) and transferrin (Tf) as ligands. The developed NPs were characterized for different physicochemical parameters and stability. The in vivo biodistribution showed preferential targeting to brain and reduced accumulation in non-target organs over a prolonged duration of time. Finally, partial sciatic nerve injury model was used to demonstrate the increased pharmacodynamic response as antinociceptive effect. Both biodistribution and pharmacodynamic study in mice confirmed that the approach used for LTG can help to increase clinical applications of LTG due to brain targeting and reduced side effects.

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Section: Intradermal Skin Testmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protein-Functionalized PLGA Nanoparticles of Lamotrigine for Neuropathic Pain Management

et al. 2014

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“…One SJS cases was published twice (26,33), but we only included the more detailed one (26) for further analysis. Two fatal reactions were reported, one in a patient with TEN and multiple organ involvement (27) and one in another patient with a diagnosis of TEN (32).…”

Section: Published Casesmentioning

confidence: 99%

Lamotrighe‐Induced Severe Cutaneous Adverse Reactions

1998

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Summary: Purpose:We systematically reviewed and analyzed published and unpublished cases of Stevens-Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN) associated with lamotrigine (LTG) therapy to identify characteristics of these reactions.Methods: We performed a MEDLINE search (January 1985 to April 1998) and citation tracking for published reports. In addition, reports were requested from the Uppsala Monitoring Centre of the World Health Organization (WHO). Published and WHO cases of LTG-associated SJS or TEN were included if the causal relationship was assessed as either possible, probable, or definite.Results: We identified a total of 57 cases (43 cases of SJS, 14 cases of TEN), of which 13 (23%) were published. Cases in the SJS group were significantly younger-than in the TEN group (21 years vs. 31 years). The median time to onset (17 days for SJS and TEN) and the median dosage at onset (50 mg vs. 87.5 mg) for SJS and TEN did not differ significantly. Concomitant use of valproate (VPA) was reported in 74% of the SJS cases and 64% of the TEN cases. In three cases, TEN was the cutaneous manifestation of the antiepileptic drug hypersensitivity syndrome (AHS).Conclusions: The main features of severe cutaneous drug reactions, such as dosage, onset, and concomitant VPA use, do not differ in patients with LTG-induced SJS or TEN. SJS or TEN may also be the cutaneous manifestations of LTG-induced AHS. Further epidemiologic studies are needed to identify the incidence of severe LTG-induced cutaneous adverse reactions and the relative risk compared with other AEDs. Key Words: Lamotrigine-Antiepileptic drugs-Stevens-Johnson syndrome-Toxic epidermal necrolysis-Hypersensitivity .Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN, Lye11 syndrome) are severe albeit rare adverse drug reactions (ADRs) to several antiepileptic drugs (AEDs) such as phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), and valproate (VPA) (1-6). A recent cohort study indicated that the risks for severe cutaneous reactions in first-time users of PHT and CBZ are 9110,000 and 6.2/10,000, respectively (7). Severe cutaneous adverse reactions (SCARS) such as erythema multiforme (EM), SJS, or TEN may also represent the cutaneous manifestation of the antiepileptic drug hypersensitivity syndrome (AHS), which is defined by the triad of fever, a cutaneous reaction, and internal organ involvement (3,8).Lamotrigine (LTG), a phenyltriazine, is chemically unrelated to existing AEDs (9). It is extensively metabolized, predominantly by N-glucuronidation, whereas only minor fractions undergo N-oxidation and N-methylation

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“…In this paper we focus on allergic drug‐reactions, which account for about one‐seventh of all adverse drug reactions [1] but represent a major problem of drug safety because of their potential severity and unpredictability [2–4]. Due to the clinical and histological similarities between drug‐allergic skin eruptions and graft‐vs.‐host disease it has been hypothesized that cutaneous drug‐induced reactions represent specific immune responses of T cells against antigens (drugs) that are bonded to the surface proteins of keratinocytes [5–8].…”

Section: Introductionmentioning

confidence: 99%