Small occasional doses of azelastine nasal spray would not be expected to cause any adverse effects in breastfed infants. Larger doses or more prolonged use of the nasal spray may cause drowsiness and other effects in the infant or decrease the milk supply, particularly in combination with a sympathomimetic such as pseudoephedrine or before lactation is well established. Infant rejection of the breast might occur because of the bitter taste of the drug. The oral, nonsedating antihistamines are preferred alternatives. Because absorption from the eye is limited, azelastine would not be expected to cause any adverse effects in breastfed infants. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue.

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by a lack of targetable receptors, leading to limited treatment options and a critical need for novel therapeutic strategies. This study aimed to evaluate the potential of azelastine, a clinically approved H1-antihistamine, for drug repositioning against TNBC and to elucidate its underlying HRH1-independent mechanism of action. Cell viability assays (CCK-8) were performed on TNBC cell lines (MDA-MB-231 and BT-549) following treatment with azelastine and its major metabolite, desmethyl azelastine. After observing ambiguous clinical associations between HRH1 expression and patient prognosis, HRH1 dependency was assessed through histamine stimulation and HRH1 knockdown (siRNA). Subsequently, the role of ADP-ribosylation factor 1 (ARF1), found to be overexpressed in TNBC and linked to poor prognosis, was investigated using ARF1 knockdown (siRNA), co-treatment with the Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) inhibitor golgicide A (GCA), and co-treatment with the Drp1 inhibitor M-divi 1. Azelastine and desmethyl azelastine potently reduced MDA-MB-231 cell viability in a dose- and time-dependent manner, achieving cell survivals of 61.3 ± 6.1% (30 µM) and 34.9 ± 3.7% (50 µM) for azelastine, and 52.4 ± 12.5% (30 µM) for desmethyl azelastine, respectively, after 72 h, with an IC50 of 35.93 µM determined for azelastine in MDA-MB-231 cells. Additionally, azelastine significantly reduced the viability of BT-549 cells. Bioinformatic analysis of clinical datasets revealed HRH1 downregulation in tumors and, functionally, neither histamine stimulation nor HRH1 knockdown mediated azelastine cytotoxicity in cell culture. Importantly, ARF1 expression was significantly upregulated in TNBC and associated with poor prognosis. Co-treatment with GCA, preventing ARF1 activation, restored viability to near-control levels, supporting dependence on the GBF1-ARF1 activation axis of azelastine, whereas the Dynamic-related protein 1 (Drp1) inhibitor M-divi 1 not only partially rescued CCK-8-based cell viability but also normalized azelastine-induced loss of MitoTracker™ Red CMXRos signal and partially preserved (4',6-diamidino-2-phenylindole) DAPI-based cell density, indicating Drp1-dependent mitochondrial dysfunction. Furthermore, azelastine selectively reduced p-ERK phosphorylation in the cell signaling pathway. Azelastine exerts potent anticancer effects in TNBC cells via an HRH1-independent, ARF1-dependent mechanism that attenuates the Extracellular signal-regulated kinase (ERK)-Drp1 axis, and induces Drp1-dependent mitochondrial dysfunction, independent of its canonical HRH1 receptor function. This ARF1-dependent mechanism provides strong scientific rationale for the drug repositioning of azelastine as an effective therapeutic agent for ARF1-driven TNBC.

We report the case of a 34-year-old female who presented with headaches, visual disturbances, and unsteadiness, mostly triggered by head rotation. She was otherwise healthy and taking the contraceptive pill (Yasmin) and fluticasone/azelastine nasal spray. Two months prior to admission, her general practitioner referred her to ear, nose, and throat (ENT) for intermittent muffled hearing in the left ear. ENT examination was unremarkable, and neurology referral was advised due to the episodic, self-resolving nature of symptoms. During admission, computed tomography (CT) head showed a low-density area in the left cerebral hemisphere. Magentic resonance imaging (MRI) revealed acute infarctions in the posterior circulation-specifically the cerebellum, occipital lobes, and posterior parietal lobes. A repeat MRI 48 h later showed a new right occipital infarct. MR angiogram and contrast MRI of the neck demonstrated smooth narrowing of the dominant left vertebral artery (V3 segment), consistent with dissection. Workup for secondary causes was normal. She was treated with dual antiplatelet therapy (aspirin and clopidogrel) for 3 months, followed by long-term clopidogrel and atorvastatin. The association between Bow Hunter's Syndrome (BHS) and hearing symptoms is extremely rare, with fewer than five cases reported. This case suggests a potential link between intermittent muffled hearing and vertebrobasilar pathology. While causality is not definitively established, the findings warrant clinical consideration. Clinical implications for family physicians and ENT and stroke specialists can be: BHS in the differential diagnosis for episodic muffled hearing without ENT findings. Watch for associated symptoms (e.g., dizziness, neck pain, visual changes). Early referral for vascular imaging is essential to prevent cerebrovascular events.

Allergic rhinitis (AR) is a common chronic respiratory disease that significantly impairs the life of children. While a combination intranasal spray of azelastine hydrochloride and fluticasone propionate (Aze-Flu) is an established effective treatment for adults with moderate-to-severe AR, the clinical evidence available in the pediatric population is limited. This review summarizes the current evidence on the efficacy, safety, and impact on Quality of Life (QoL) of Aze-Flu in children. Clinical trials have demonstrated that Aze-Flu provides faster and greater symptom relief in children with AR compared to fluticasone propionate (FP) monotherapy. One randomized controlled trial demonstrated that, although the overall change in the reflective Total Nasal Symptom Score (rTNSS) was not statistically different from the placebo, this was possibly due to rater assessment bias. Children's symptoms self-assessment showed considerable ameliorations in both nasal and ocular scores. Furthermore, treatment with Aze-Flu has been shown to produce clinically relevant and statistically significant improvements in QoL compared to placebo in children with moderate-to-severe seasonal AR. The safety profile is favorable; a 3-month study confirmed that Aze-Flu is well-tolerated, with an incidence of treatment-related adverse events comparable to that of FP monotherapy. Beyond AR, emerging evidence suggests potential benefits of Aze-Flu in children with adenoid hypertrophy. The available evidence supports Aze-Flu as an effective and well-tolerated therapeutic option for children with moderate-to-severe AR, offering superior and faster symptom control than monotherapy and leading to meaningful improvements in quality of life. Future pediatric trials should incorporate validated, child-specific assessment tools to better capture treatment efficacy.

Renal and testicular toxicities are side effects of the chemotherapeutic agent cisplatin (Cis). The study aims to assess the potential repurpose of Azelastine (Az), an H1-receptor antagonist to alleviate Cis-induced toxicity.

An essential step in the life cycle of human immunodeficiency virus type 1 (HIV-1) is the packaging of tRNA3Lys during viral assembly. This step, which requires the assembly of a ternary complex consisting of GagPol, mitochondrial lysyl-tRNA synthetase, and tRNA3Lys, is essential for the production of infectious viruses. Indeed, it allows the initiation of reverse transcription in the particles. In this work, we used an in vitro assay to isolate molecules from a chemical library that disrupt the interaction between the integrase domain of GagPol and mitochondrial lysyl-tRNA synthetase. The three selected molecules also inhibit HIV-1 replication in an ex vivo assay. The number of HIV-1 particles produced in the presence of the drugs is greatly reduced, with a half-maximal inhibitory concentration obtained at a drug concentration of 5 µM. In addition, we have shown that the few particles produced in the presence of the drugs exhibit significantly reduced infectivity, due to their inability to synthesize minus-strand strong stop cDNA. In parallel, the tRNA3Lys content of the particles obtained in the presence of drugs decreased significantly. The inability to package tRNA3Lys into virions results in replication-defective particles.IMPORTANCESeveral families of inhibitors have been selected to tackle the human immunodeficiency virus (HIV). Cell entry, reverse transcriptase, integrase, or protease is the most popular targets along the viral life cycle. During the budding step of the virus, the packaging of tRNA3Lys into particles, which serves as a primer for the initiation of reverse transcription in the virus, has been shown to be essential for the production of infectious virions. In this study, we isolated molecules that inhibit viral replication by inhibiting the incorporation of tRNA3Lys into virions. The inhibitors of HIV-1 replication described in this work demonstrate that the HIV-1 tRNA packaging step can be exploited for the development of a new family of drugs with novel resistance profiles.

Linezolid is an antibiotic of the oxazolidinone class which is highly effective in the treatment of serious Gram-positive infections. It is usually well tolerated, but rare adverse reactions like angioedema have been reported. This case report investigates the occurrence of eyelid angioedema induced by linezolid. The patient, a man in his early 70s with sepsis and cellulitis caused by Streptococcus pyogenes, developed bilateral eyelid angioedema after receiving a second dose of linezolid. The drug was discontinued and supportive treatment with methylprednisolone and azelastine eye drops resolved the symptoms within 72 hours. The temporal link between drug administration and eyelid oedema supports linezolid as the likely trigger, confirmed by the Karch-Lasagna and Naranjo algorithms.