Safety of Eslicarbazepine Acetate in Elderly Versus Non-Elderly Patients with Focal Seizures: From Pooled Data of Clinical Studies to 8 Years of Post-Marketing Experience

Background Safety data on routine clinical use of gadoxetate disodium in elderly patients is not reported yet. Purpose To assess the safety of liver specific gadoxetate disodium in contrast enhanced magnetic resonance imaging in elderly patients (≥65 years) in comparison to adults (18–64 years). Material and Methods Safety data on gadoxetate disodium were analyzed from 12 clinical phase II–III studies and from our pharmacovigilance database. A comparison between elderly (≥65 years) versus adults (18–64 years) was performed with respect to the frequency of drug-related adverse events (AEs) in clinical phase II–III studies and adverse drug reactions (ADRs) in the pharmacovigilance database. Results In clinical studies, 1989 patients were enrolled: 675 elderly and 1314 adults. Twenty-three elderly patients (3.4%) suffered at least one drug-related AE in contrast to 58 patients (4.4%) in the group of adults (odds ratio = 0.76; 95% confidence interval = 0.45–1.27). Since marketing authorization in 2004, more than 3.5 million patients have been exposed to gadoxetate disodium worldwide: 1.7 million (48.6%) in elderly and 1.8 million (51.4%) in adults. The number of patients with post-marketing ADRs (total n = 793) was 354 (0.021%) in the elderly group and 439 (0.024%) in the adult group. Thus, there were significantly fewer patients with ADRs reported in the group of elderly versus adults ( P = 0.028). Hypersensitivity/immune system disorders, gastrointestinal disorders, and respiratory disorders were the most frequent ADRs in both groups, elderly and adults. Conclusion The incidence of drug-related AEs in clinical studies was similar and that of patients with ADRs in the post-marketing setting was lower in elderly (≥65 years) compared with younger adults aged 18–64 years. Overall, gadoxetate disodium shows a favorable safety profile in both age groups.

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Safety and Tolerability of Adjunctive Eslicarbazepine Acetate in Pediatric Patients (Aged 4-17 Years) With Focal Seizures

Journal of Child Neurology ◽

10.1177/0883073819890997 ◽

2019 ◽

Vol 35 (4) ◽

pp. 265-273 ◽

Cited By ~ 4

Author(s):

Mark Mintz ◽

Jesus E. Pina-Garza ◽

Steven M. Wolf ◽

Patricia E. McGoldrick ◽

Sergiusz Józwiak ◽

...

Keyword(s):

Adverse Events ◽

Pediatric Patients ◽

Safety Data ◽

Adjunctive Treatment ◽

Eslicarbazepine Acetate ◽

Serious Adverse Events ◽

Double Blind ◽

Focal Seizures ◽

Clear Dose Response ◽

Cluster Seizures

Objective: To evaluate the safety and tolerability of adjunctive eslicarbazepine acetate (ESL) in pediatric patients (aged 4-17 years) with refractory focal seizures. Methods: Pooled safety data from patients aged 4-17 years in Study 208 (NCT01527513) and Study 305 (NCT00988156) were analyzed. Both were randomized, double-blind, placebo-controlled studies of ESL as adjunctive treatment in pediatric patients with refractory focal seizures receiving 1 or 2 antiepileptic drugs. Incidences of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), TEAEs leading to discontinuation, and TEAEs of special interest were evaluated. Results: The safety population comprised 362 patients (placebo, n = 160; ESL, n = 202). The overall incidence of TEAEs was similar between the ESL (67.8%) and placebo groups (65.6%), with no clear dose-response relationship. The most frequently reported TEAEs with ESL were headache, somnolence, vomiting, and diplopia. Overall incidences of SAEs and TEAEs leading to discontinuation were higher with ESL versus placebo (9.9% vs 5.0% and 5.9% vs 2.5%, respectively). The majority of SAEs with ESL occurred in Study 305. Two deaths were reported, 1 with ESL (0.5%) due to cluster seizures (resulting in herniation of the cerebellar tonsils) and 1 with placebo (0.6%) due to asphyxia. TEAEs related to allergic reaction, hyponatremia, hypothyroidism, cytopenia, seizure exacerbation, cognitive dysfunction, psychiatric disorders, or suicide occurred infrequently (<9%). Conclusion: Adjunctive ESL was generally well tolerated in children aged 4-17 years with focal seizures. The safety profile of ESL in children was comparable to that observed in adults.

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Weekly Low Dose Epirubicin in Elderly Cancer Patients

Tumori Journal ◽

10.1177/030089169608200414 ◽

1996 ◽

Vol 82 (4) ◽

pp. 369-371 ◽

Cited By ~ 10

Author(s):

Dario Nicolella ◽

Giuseppe Grimaldi ◽

Giuseppe Colantuoni ◽

Mario Belli ◽

Giuseppe Frasci ◽

...

Keyword(s):

Side Effects ◽

Elderly Patients ◽

Cancer Patients ◽

Combination Chemotherapy ◽

Clinical Studies ◽

Low Dose ◽

Performance Status ◽

Elderly Cancer Patients ◽

Grade 3 ◽

Severe Mucositis

Aims and background The treatment of elderly patients with metastatic solid tumours is still a debated problem. Patients over 75 years are generally excluded from combination chemotherapy trials because of higher toxicity. Several clinical studies have shown that weekly low dose epirubicin is a well tolerated and effective treatment for elderly cancer patients (breast, prostate, lung). Methods We report a study of patients aged between 75 and 85 years affected by metastatic anthracyclines-sensible carcinomas, to assess the tolerance of epirubicin given weekly at a dose of 25 mg/m2. Results 25 patients (13 males, 12 females; ECOG P.S. 0-2) entered the study and were evaluable for side effects. One-hundred and ninety-six cycles of therapy have been administered. Side effects were never severe. Mucositis (9 patients), leucopenia (7 patients), anemia (5 patients) were usually of grade 1 or 2. Grade 1 cardiotoxicity (tachycardia) was observed in only one case. Grade 3 toxicity consisted in anemia (1 patient) and mucositis (1 patient), while grade 4 toxicity never occurred. Nineteen patients were evaluable for response: 0 CR, 4 PR (1 lung, 3 breast), 8 SD (3 lung, 3 breast, 2 prostate) have been observed. Compliance was encouraging and the majority of patients showed a decrease in symptoms and an improvement in performance status. Conclusions Weekly low-dose epirubicin is a very well tolerated treatment in elderly cancer patients. In view of the negligible toxicity encountered, it could be of utility to test this regimen in patients aged 75 years or older, affected by anthracyclines-sensible metastatic tumors, also to assess activity.

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