Vemurafenib-Induced DRESS

Wenk, Kurt S.; Pichard, Dominique C.; Nasabzadeh, Teresa J.; Jang, Sekwon; Venna, Suraj

doi:10.1001/jamadermatol.2013.5278

Cited by 36 publications

(25 citation statements)

References 7 publications

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“…Overall, these results suggest that the feasibility of vemurafenib monotherapy should not be rejected based on poor PS alone. However, given the rapid onset of grade≥2 skin rash, the fragile patients should be closely monitored during the first month of treatment, especially to evaluate the severity of the rash and the absence of criteria for severe skin adverse reaction such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) [16,17]. In our study, median vemurafenib concentration and its interindividual variability are in accordance with those previously published in a phase 1 study [5].…”

Section: Discussionsupporting

confidence: 87%

Vemurafenib pharmacokinetics and its correlation with efficacy and safety in outpatients with advanced BRAF-mutated melanoma

et al. 2015

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Vemurafenib is a BRAF kinase inhibitor approved for first-line treatment of metastatic BRAF (V600) -mutant melanoma. However, data on the pharmacokinetic/pharmacodynamic (PK/PD) relationship are lacking. The aim of this prospective, multicenter study was to explore the PK/PD relationship for vemurafenib in outpatients with advanced BRAF-mutated melanoma. Fifty-nine patients treated with single-agent vemurafenib were prospectively analyzed. Vemurafenib plasma concentration (n = 159) was measured at days 15, 30, 60, and 90 after treatment initiation. Clinical and biological determinants (including plasma vemurafenib concentration) for efficacy and safety were assessed using Cox's model and multivariate stepwise logistic regression. Median progression-free survival (PFS) and overall survival were 5.0 (95 % confidence interval [95 % CI] 2.0-6.0) and 11.0 (95% CI 7.0-16.0) months, respectively. Twenty-nine patients (49 %) experienced any grade ≥3 toxicity and the most frequent grade ≥2 toxicity was skin rash (37 %). Severe toxicities led to definitive discontinuation in seven patients (12 %). Grade ≥2 skin rash was not statistically associated with better objective response at day 60 (p = 0.06) and longer PFS (hazard ratio 0.47; 95 % CI 0.21-1.08; p = 0.075). Grade ≥2 skin rash was statistically increased in patients with ECOG ≥ 1 (odds ratio 4.67; 95 % CI 1.39-15.70; p = 0.012). Vemurafenib concentration below 40.4 mg/L at day 15 was significantly associated with a shorter PFS (1.5 [0.5-5.5] vs. 4.5 [2-undetermined] months, p = 0.029). Finally, vemurafenib concentration was significantly greater in patients developing grade ≥2 rash (61.7 ± 25.0 vs. 36.3 ± 17.9 mg/L, p < 0.0001). These results suggest that early plasma drug monitoring may help identify outpatients at high risk of non-response or grade ≥ 2 skin rash.

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Section: Discussionsupporting

confidence: 87%

Vemurafenib pharmacokinetics and its correlation with efficacy and safety in outpatients with advanced BRAF-mutated melanoma

et al. 2015

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“…The main drugs involved are anticonvulsants and allopurinol. It has recently been shown that certain viruses (HHV-6, EBV, CMV) are involved in the appearance of the reaction [3]. No viral reactivation was observed in the present case.…”

Section: Discussionsupporting

confidence: 51%

“…In the other 2 cases of induced DRESS previously reported in the literature, lesion onset occurred early but later than in the present patient. The first case [3] consisted in a female patient, aged 80 years, with DRESS syndrome appearance 3 weeks after vemurafenib initiation. The second case [4] consisted in a male patient, aged 69 years, with DRESS syndrome development 4 weeks after vemurafenib initiation.…”

Section: Discussionmentioning

confidence: 99%

“…Severe drug eruptions on vemurafenib are exceptional. The principal cutaneous toxicity induced by vemurafenib is maculopapular rash, which has been reported in 36-68% of patients and was in the majority of cases of grade ≤3 [3,5]. The only severe drug eruptions previously reported with vemurafenib, other than the 3 cases of DRESS, consist in 3 cases of toxic epidermal necrolysis [6,7,8] and 1 case of Stevens-Johnson syndrome [7].…”

Section: Discussionmentioning

confidence: 99%

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Early-Onset Vemurafenib-Induced DRESS Syndrome

et al. 2015

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Vemurafenib is a BRAF inhibitor indicated in metastatic or unresectable melanoma in patients with BRAF mutations. Vemurafenib is frequently toxic, but the toxicity is often not serious. The third case of vemurafenib-induced drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is reported herein. The case is unusual in that the onset was early, with symptoms emerging as of day 8 of treatment. Treatment of DRESS syndrome is not currently based on precise recommendations, but systemic corticosteroid therapy is effective in serious cases. Severe toxidermias under vemurafenib are exceptional; immediate discontinuation of treatment upon diagnosis is imperative. Switching from vemurafenib to dabrafenib then seems to constitute an interesting therapeutic alternative, since its efficacy is the same but with fewer cutaneous adverse reactions. This case highlights the importance of awareness of the risk of DRESS syndrome associated with vemurafenib and monitoring for warning signs from treatment initiation.

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“…Aromatic anticonvulsants (phenytoin, phenobarbital, carbamazepine) and sulphonamides are the most common causative drugs, but a variety (18,(20)(21)(22)(23)(24)(25)(26)(27). Lamotrigine [6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine] is an antiepileptic drug, used in the management of a broad range of seizures in adults and children which is not an aromatic antiepileptic, thus being structurally and pharmacologically unrelated to other antiepileptic medications e.g.…”

Section: Discussionmentioning

confidence: 99%

Lamotrigine Associated DRESS Syndrome – a Case Report

Balaban

Ninković-Baroš

2015

Serbian Journal of Dermatology and Venereology

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before admission to our Clinic, because of persistent symptoms of high fever (body temperature above 38°C), severe nonproductive cough, nasal secretion, facial swelling, especially around the nose, and erythema on the hands. A diff erential white blood cell count and urinalysis were performed, and except mild eosinophilia of 6% (normal range 0 -5%) all other fi ndings were within normal limits. She was advised to stop taking all drugs. Th e patient was using three drugs (olanzapine: an antipsychotic serotonin blocker; lamotrigine: an antiepileptic and mood stabilizer; and losartan: an antihypertensive and angiotensin II receptor blocker), since she was discharged from the Clinic of Psychiatric Diseases a month before, where she was hospitalized under the diagnosis of paranoid personality disorder. Due to persistent high temperature and worsening of respiratory symptoms, the patient was examined by the specialist for infectious diseases, who set the diagnosis of acute bronchiolitis, and introduced azithromycin 500 mg once daily D rug-induced delayed multiorgan hypersensitivity syndrome (DIDMOHS) (1), also known as drug rash (reaction) with eosinophilia and systemic symptoms (DRESS) syndrome, is a severe, unexpected drug reaction which aff ects several organ systems at the same time (2, 3, 4). Most commonly it causes a combination of high fever, morbiliform skin rash and infl ammation of one or more internal organs including the liver, kidneys, lungs and/or heart. It generally starts two to eight weeks after taking the off ending medicine. Th e drugs most often reported with DRESS include anticonvulsants (particularly those with aromatic structures), sulfa derivatives, antidepressants, non-steroidal anti-infl ammatory drugs, and antimicrobials (5, 6, 7). Case reportWe present a 44-year-old unemployed nurse with psychiatric history since her teens. She was fi rst admitted to the Emergency Department seven days AbstractDrug-induced delayed multiorgan hypersensitivity syndrome, also known as drug rash (reaction) with eosinophilia and systemic symptoms (DRESS) syndrome, represents a drug-induced cluster of skin, hematologic and systemic symptoms. More than forty drugs have been associated with this syndrome. We present a case of DRESS syndrome suspecting that lamotrigine was directly responsible for the patient's rash and other symptoms. A female patient presented with extensive skin rash, fever, hematologic abnormalities, organ involvement such as hepatitis, pancreatitis and respiratory symptoms. The symptoms developed four weeks after the initiation of the offending drug, and disappeared eight weeks after its discontinuation.

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Vemurafenib-Induced DRESS

Cited by 36 publications

References 7 publications

Vemurafenib pharmacokinetics and its correlation with efficacy and safety in outpatients with advanced BRAF-mutated melanoma

Vemurafenib pharmacokinetics and its correlation with efficacy and safety in outpatients with advanced BRAF-mutated melanoma

Early-Onset Vemurafenib-Induced DRESS Syndrome

Lamotrigine Associated DRESS Syndrome – a Case Report

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