As the first treatment approved for fibromyalgia in 15 years, sublingual cyclobenzaprine (TONMYA®) is a useful addition to treatment options for adults in the USA. Sublingual cyclobenzaprine represents a novel treatment approach that targets disturbed sleep whilst improving fibromyalgia symptoms. Sublingual administration produces diurnal fluctuations in cyclobenzaprine plasma concentrations, with peak plasma concentrations coinciding with the middle of the sleep phase. As demonstrated in placebo-controlled, phase III clinical trials in adults with fibromyalgia, sublingual cyclobenzaprine 5.6 mg once daily at bedtime reduces pain and improves patient-reported symptoms, including sleep quality and fatigue. Sublingual cyclobenzaprine is generally well tolerated, with the most common treatment-emergent adverse events (AEs) being oral mucosal reactions. In clinical trials, treatment with sublingual cyclobenzaprine was not associated with AEs commonly reported with other fibromyalgia therapies. Characterized by widespread pain, sleep disturbances, and fatigue, fibromyalgia is a complex chronic pain condition with incompletely understood mechanisms. Established treatments for fibromyalgia primarily target pain relief; although, many patients discontinue these treatments due to adverse events (AEs) or a lack of efficacy. Recently, development of new therapies has targeted improvements in sleep quality to improve fibromyalgia symptoms. Oral cyclobenzaprine formulations improved sleep quality in clinical trials but demonstrated limited efficacy for pain relief and were associated with AEs such as fatigue. Sublingual cyclobenzaprine (TONMYA®) was recently approved in the USA for the treatment of fibromyalgia in adults. With sublingual administration, cyclobenzaprine concentrations peak during the sleep phase and fall during the daytime. As demonstrated in phase III clinical trials, sublingual cyclobenzaprine 5.6 mg once daily at bedtime reduces pain and improves patient-reported symptoms, including sleep quality and fatigue. Sublingual cyclobenzaprine is generally well tolerated. The most common treatment-emergent AEs are oral mucosal reactions. As the first treatment approved for fibromyalgia in 15 years, sublingual cyclobenzaprine is a useful addition to treatment options for adults with fibromyalgia in the USA.
Endometriosis is a chronic, relapsing inflammatory disease requiring sustained hormonal suppression, yet first-line management remains dominated by daily oral progestins designed for short-acting use. Although pharmacologically effective, long-term outcomes are frequently compromised by fluctuating exposure, tolerability-driven discontinuation, and poor persistence. This narrative comparative review examines first-line progestins across efficacy, safety, tolerability, and persistence, alongside long-acting platforms including intrauterine systems, vaginal rings, implants, injectables, and emerging depots. Relevant clinical, pharmacokinetic, adherence, formulation, and preclinical evidence was identified through iterative literature searches. By synthesizing clinical, pharmacokinetic, and adherence evidence within a unified translational framework, we identify formulation-driven gaps that may influence exposure stability and therapeutic durability. The analysis distinguishes delivery-modifiable constraints from biological limitations such as progesterone resistance and disease heterogeneity, and outlines priorities for next-generation formulation development. Aligning delivery architecture with disease chronicity may offer a pragmatic, scalable, and clinically impactful pathway to strengthen established progestin therapies while complementing molecular innovation. Interpretation is limited by heterogeneity in study populations, endpoints, and treatment durations, and by limited endometriosis-specific clinical evidence for several emerging delivery platforms.
Menopausal vasomotor symptoms (VMS) are common and can substantially impair health-related quality of life through negative effects on sleep, mood, cognition, daily activities and long-term health outcomes. Menopausal hormonal therapy (MHT) is the first-line treatment for VMS in patients aged < 60 years and within 10 years of menopause onset. Decisions regarding MHT use and formulation should be individualised to each patient according to age, symptoms, time since menopause onset and individual risk factors and medical history. For patients in whom MHT is contraindicated or not preferred, non-hormonal drugs, such as paroxetine, fezolinetant and elinzanetant, offer effective alternative treatment options. Although several non-hormonal drugs are used off label to treat VMS, novel non-hormonal drugs are under investigation and may further expand treatment options.
Combined hepatocellular–cholangiocarcinoma (cHCC-CCA) is a rare liver cancer characterized by cancerous cells of bile duct origin. Treatment options are limited and prognosis is poor. When a mutation of isocitrate dehydrogenase-1 (IDH1) is present, the patient may be eligible for treatment with ivosidenib, an IDH1 inhibitor. Ivosidenib improved overall survival versus placebo in patients with previously treated advanced CCA with IDH1 mutation in the ClarIDHy phase III trial. We describe the case of a male patient aged 55 years diagnosed with cHCC-CCA with an IDH1 pathogenic mutation who failed first-line treatment with cisplatin plus gemcitabine. Ivosidenib 500 mg once daily treatment was initiated, and after 3 months, partial regression of the target lesion was observed, and after 22 months, best overall response was partial remission. No adverse events were reported. After 35 months, the patient continued to receive ivosidenib since the target lesion had not progressed, and treatment was very well tolerated. Ivosidenib appeared to be an effective and well-tolerated treatment for this patient with previously treated cHCC-CCA who had IDH1 mutations.
Fluoroquinolones have been associated with certain injuries of tendon, muscles and synovium (MTS), but the comparative risk relative to other antibiotics remains limited. The aim of this study was to examine the association between newly prescribed fluoroquinolones and the occurrence of MTS injuries with focus on length of follow-up, active comparators, age and gender. This is a cohort study in active comparator new-user design based on data from the German statutory health insurance “Allgemeine Ortskrankenkasse” (AOK), 2013–2019. Fluoroquinolones were compared with eight comparator antibiotic agents. Adults with incident antibiotic prescription during 2014–2018 covered by the German statutory health insurance, called “Allgemeine Ortskrankenkasse” (AOK) were followed up during the 365 days after antibiotic exposure. The primary outcome was the occurrence of incident MTS injuries. Hazard ratios with corresponding 95
