Summary

• Serious drug-induced skin reactions include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), generalized bullous fixed drug eruption (GBFDE), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS).¹
• Two case reports were identified of patients on of INVEGA SUSTENNA experiencing a serious skin reaction. One reported a case of TEN and the other reported a case of erythema multiforme.^2,3

BACKGROUND

TEN is a rare, severe mucocutaneous reaction characterized by extensive necrosis and epidermal detachment of >30% of the body surface area. A clinical diagnosis must be confirmed by skin biopsy showing epidermal necrosis and must be differentiated from erythema multiforme which is infectious in nature and carries a better prognosis. TEN is associated with a 20-25% mortality rate and nearly 50% sequelae, primarily ophthalmological in nature.²

CLINICAL STUDIES

Toxic Epidermal Necrolysis (TEN)

Struye et al (2016)² described a case of TEN in a 24-year-old male Filipino patient in Belgium receiving INVEGA SUSTENNA. The patient was diagnosed with paranoid schizophrenia at the age of 21 and treated with oral paliperidone 6 mg/day for one month while hospitalized. He was noncompliant upon discharge. Upon rehospitalization at the age of 24, he was placed on INVEGA SUSTENNA (234 mg on January 8, 2015; 156 mg on January 15, 2015) following 10 days of oral paliperidone. Concomitant medications included olanzapine 10 mg/day and clorazepate 5 mg/day. On February 2, 2015, the patient experienced a low-grade fever (100.04°F) accompanied by a pruriginous rash that appeared on his chest and arms. The rash subsided following initiation of levocetirizine 5 mg nightly for 5 days and 32 mg methylprednisolone for 3 days. The patient was then prescribed mometasone cream, levocetirizine, ranitidine and paracetamol when the rash worsened on February 7, 2015. Due to the spread of the rash, all psychotropic medications were discontinued on February 11, 2015, including the INVEGA SUSTENNA injection scheduled for February 12^th. The patient received treatment consisting of a methylprednisolone infusion, ranitidine, clobetasol propionate and paracetamol. Generalized erythroderma (>90% cutaneous surface involvement) with diffuse detachment and positive Nikolsky sign (skin peeling caused by pressure/slight rubbing of the skin at the base of the lesion), red eyes and bleeding lips were observed five days later. The patient was transferred to the burn unit on February 17, 2015, and diagnosed, via biopsy analysis, with TEN. Symptoms and treatments over the next several weeks included the following: sedation, intubation and mechanical ventilation, daily antiseptic dressings, ocular dexamethasone and tobramycin cream and three days of intravenous immunoglobulin. Over the next month and a half, evolution of skin lesions was favorable with a few depigmentation spots as sequelae. The patient experienced three septic shocks and severe diarrhea due to cytomegalovirus enterocolitis and TEN induced intestinal mucosal damage, insulin-dependent diabetes of unclear origin, extreme weight loss (admission: 171.6 lb; hospital discharge: 127.6 lb) and acute renal failure (with favorable outcome) due to dehydration and ganciclovir. He was reintroduced to olanzapine 10 mg/day without reappearance of rash and transferred to another university hospital on April 8, 2015.

Erythema Multiforme

Sundling and Held (2017)³ described a case of edematous erythematous rash in a 64-year-old male patient receiving INVEGA SUSTENNA. The patient had a history of schizoaffective disorder, cannabis use disorder, and adjustment disorder. He was admitted to the hospital following an attempted suicide by ingestion of clonazepam 12 mg. Current medications included lamotrigine and venlafaxine which were both discontinued on hospital day 2 due to antipsychotic preference. On day 3 the patient was initiated on oral paliperidone. Following 6 days of treatment without incident, INVEGA SUSTENNA 234 mg was administered. On day 12, the patient developed a small abdominal rash and was treated with oral antihistamines and topical corticosteroids. However, the rash worsened, requiring a dermatology consult on day 14. Oral paliperidone was discontinued and the second INVEGA SUSTENNA initiation dose was held. The patient went on to develop shortness of breath, hypotension, tachycardia and diaphoresis. He was prescribed prednisone for 2 weeks in addition to hydroxyzine, famotidine and topical triamcinolone. A skin biopsy ruled out Steven Johnson’s Syndrome and TEN and confirmed erythema multiforme and urticaria. The rash continued to improve and was completely resolved prior to discharge on hospital day 23. Due to the time of onset, skin biopsy results and lack of other recent medication changes, the authors deemed INVEGA SUSTENNA as the cause of the patient’s severe rash (Naranjo Adverse Drug Reaction Probability Scale score: 6). They did note that they were unable to determine if the rash would have appeared with longer oral paliperidone tolerability trial period.

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 12 December 2024.