Identification of unknown impurities J, RRT 2.2, 2.4, 2.6 and 3.4 in tetralysal® capsules.

Tetralysal® is a Galderma oral drug product (DP) marketed for the treatment of acne. Tetralysal® is sold in capsules containing either 150 mg or 300 mg of the drug substance. In the British Pharmacopoeia monograph for Lymecycline Capsules, the impurities already specified in the drug substance (A-G), visible in the European Pharmacopoeia 〈1654〉, are also specified together with an unidentified impurity at RRT 1.6 (Impurity J). Based on both monographs Galderma has focused on characterizing most of specified and unspecified impurities to better understand the stability and degradation processes of the formulation. In this manuscript, through both formal synthesis, preparative LCMS and formal degradation studies, we are the first group to confirm the structural identities of 5 unidentified impurities (Impurity J (RRT 1.6), RRT 2.2, 2.4, 2.6 and 3.4), conditions which exacerbate the formation of all 5 impurities and response factors for RRT 2.2, 2.6 and 3.4.

Comparison between lymecycline with multidrug therapy and standard multidrug regimen (WHO-MDT) in the treatment of multibacillary leprosy patients: a retrospective cohort study.

BACKGROUND: Hansen's disease or leprosy is a chronic, infectious disease that has locally and globally afflicted all populations. Despite standard treatment with multidrug therapy (WHO-MDT), the incidence of drug resistance has been an increasingly prevalent global problem in leprosy management. This study compared the effectiveness between lymecycline with WHO-MDT and standard WHO-MDT in leprosy treatment. METHODS: The research is a retrospective cohort study at a tertiary hospital from January 2011 to July 2021. Pre- and post-treatment bacillary index, presence of new lesions, nerve function impairment, and leprosy reactions were obtained through chart review. RESULTS: The results showed a significant difference in bacteriological index (BI) in both groups at the end of the treatment. However, a higher reduction in BI was noted for the lymecycline group. For the group that took WHO-MDT alone, BI decreased by 0.7 (P < 0.001) whereas patients who took lymecycline and WHO-MDT had a BI difference of 3 (P < 0.001) upon completion of treatment. A significant decrease in the recurrence of lesions (P = 0.006) and nerve function impairment (P = 0.038) was also noted in the lymecycline group whereas there was no significant difference in leprosy reactions between the two groups. CONCLUSION: Lymecycline 600 mg daily for 3 months can be used as an adjunct in cases of leprosy resistance and treatment failure among multibacillary patients. Lymecycline significantly reduced bacillary index, recurrence of skin lesions, and nerve function impairment through its possible immunomodulatory, antiapoptotic, and neuroprotective effects.

Completion of the impurity profile of lymecycline: Formal identification of impurities E and F.

Lymecycline is the drug substance (DS) used in the Galderma drug product Tetralysal® capsules with 7 impurities currently described in the pharmacopeia labelled as A-G. In the current monograph, the structural identity of all impurities except E and F have been formally identified. In this manuscript, through both formal synthesis and preparative chromatography, we are the first group to confirm the structural identity, response factor of Impurity F and conditions which exacerbate the formation of both impurities.

Treatment of hidradenitis suppurativa with tetracycline, doxycycline, or lymecycline: a prospective study.

AIM: To evaluate the clinical efficacy of tetracycline, doxycycline, and lymecycline in patients with hidradenitis suppurativa (HS). METHODS: A prospective study of three different treatment regimens in patients with HS; oral tetracycline 500 mg twice daily, oral doxycycline 100 mg twice daily, and oral lymecycline 300 mg twice daily were administered in patients with HS. Outcomes were change in Hidradenitis Suppurativa Score (HSS), Dermatology Life Quality Life index (DLQI), overall disease-related distress, boil-related pain, number of boils in the preceding month, fraction of patients with no boils in the preceding month, and Physician's Global Assessment (PGA) score at follow-up. RESULTS: In total, 108 patients, 73 (67.6%) women and 35 (32.4%) men, were included. Mean duration of treatment was 4.3 months. The mean HSS at baseline was 26.10 (SD 20.18) points, improving to 17.97 (SD 17.88) at follow-up, difference is 8.13 (95% CI 5.21-10.93), P < 0.0001. Highest improvement in HSS was observed in the tetracycline group. After multivariate adjustment, higher reduction in HSS was significantly associated with lower BMI, Hurley stage III, higher HSS at baseline, and higher number of boils in the preceding month at baseline. CONCLUSION: Oral treatment with tetracycline, doxycycline, and lymecycline appears effective and safe in HS patients. Tetracycline provided the greatest clinical improvement measured by HSS.

Lymecycline vs. clindamycin plus rifampicin in hidradenitis suppurativa treatment: clinical and ultrasonography evaluation.

BACKGROUND: Antibiotic therapy remains the first-line treatment for hidradenitis suppurativa (HS). However, literature data on its comparative clinical efficacy and safety are limited. AIM: To investigate the efficacy of tetracycline (lymecycline 300 mg daily) vs. the combination therapy clindamycin and rifampicin (600 mg plus 600 mg daily) by evaluating and comparing the clinical response at the end of antibiotic treatment (10 weeks). METHODS: The study retrospectively analysed 52 patients divided in two groups of 26 patients: Group A received lymecycline and Group B received clindamycin plus rifampicin for 10 weeks. Subjects had mild, moderate and severe HS. The clinical and ultrasonography extent of disease was measured by the Hurley Score, Sonographic Score of Hidradenitis Suppurativa, International Hidradenitis Suppurativa Severity Score System (IHS4), pain visual analogue scale (pain VAS) and Dermatology Life Quality Index (DLQI). The primary outcome was the clinical response at the end of the antibiotic treatment period, according to the Hidradenitis Suppurativa Clinical Response measure. RESULTS: Both groups showed a significant improvement in IHS4, pain VAS and DLQI from baseline, but this was more marked in Group A. Reductions in nodule counts were similar between the two groups, whereas the number of abscesses and draining tunnels decreased more in Group B. Disease-free survival was similar between the two groups. CONCLUSION: Lymecycline monotherapy and clindamycin plus rifampicin combination are both effective treatments for patients with moderate-severe HS. Nodular-type HS seems to respond better to lymecycline, whereas the abscess/tunnel type seems to respond better to clindamycin plus rifampicin.

Severe Papulopustular Rosacea with Demodicosis in a 47-year-old Filipino female: A case report

Introduction@# Rosacea is a chronic relapsing inflammatory facial dermatosis often characterized by flare-ups and remissions exclusively affecting the centrofacial skin.@*Case report@#This is a case of multiple symmetric intensely erythematous papules, pustules, and plaques over both cheeks in a 47-year-old Filipino female. Dermoscopy showed brown-yellowish structureless areas, straight vessels in a polygonal pattern, dilated follicles, follicular plugs, ill-defined white rosettes, and non-specific scales. Skin punch biopsy showed spongiosis of the epidermis and demodex folliculorum within the follicular infundibulum. The dermis revealed telangiectasia of blood vessels and dense inflammatory infiltrates. Hypertrophy of sebaceous lobules was also seen. The patient was initially treated with oral lymecycline 300mg twice a day for 2 weeks without improvement. Due to the persistence of centrofacial erythema, papules and pustules, the patient was given prednisone 10mg once a day for 1 month and low dose isotretinoin 10mg once a day for 8 months which resulted in significant decrease in erythema and number of existing lesions. To further decrease the inflammation con- tributed by demodex mites, permethrin 5% cream twice a day for 1 month was applied. Long-pulsed Neodymium-doped yttrium aluminum garnet (Nd:YAG) 1064 nm laser for a total of 10 sessions together with Isotretinoin 10 mg every other day effectively maintained remission for 1 year and 5 months. Gentle skin care measures, sunscreen, metronidazole 0.75% cream once a day, and desonide 0.05% cream twice a day for 1 week in cases of acute flares were maintained during the treatment course.@*Conclusion@#An armamentarium of topical and oral antibiotics, corticosteroids, isotretinoin and non-ablative long-pulsed Nd:YAG 1064 nm laser showed significant improvement in the inflammatory papules, pustules, and centrofacial erythema of rosa- cea and proves to be beneficial in the maintenance of its long-term remission.

Lymecycline reverses acquired EGFR-TKI resistance in non-small-cell lung cancer by targeting GRB2.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were first-line treatments for NSCLC patients with EGFR-mutations. However, about 30 % of responders relapsed within six months because of acquired resistance. In this study, we used Connectivity Map (CMap) to discover a drug capable of reversing acquired EGFR-TKIs resistance. To investigate Lymecycline's ability to reverse acquired EGFR-TKIs resistance, two Icotinib resistant cell lines were constructed. Lymecycline's ability to suppress the proliferation of Icotinib resistant cells in vitro and in vivo was then evaluated. Molecular targets were predicted using network pharmacology and used to identify the molecular mechanism. Growth factor receptor-bound protein 2 (GRB2) is an EGFR-binding adaptor protein essential for EGFR phosphorylation and regulation of AKT/ERK/STAT3 signaling pathways. Lymecycline targeted GRB2 and inhibited the resistance of the cell cycle to EGFR-TKI, arresting disease progression and inducing apoptosis in cancer cells. Combined Lymecycline and Icotinib treatment produced a synergistic effect and induced apoptosis in HCC827R5 and PC9R10 cells. Cell proliferation in resistant cancer cells was significantly inhibited by the combined Lymecycline and Icotinib treatment in mouse models. Lymecycline inhibited the resistance of the cell cycle to EGFR-TKI and induced apoptosis in NSCLC by inhibiting EGFR phosphorylation and GRB2-mediated AKT/ERK/STAT3 signaling pathways. This provided strong support that Lymecycline when combined with EGFR targeting drugs, enhanced the efficacy of treatments for drug-resistant NSCLC.

A double-blind randomized controlled trial on the efficacy and safety of metformin as an adjunct to lymecycline and topical adapalene plus benzoyl peroxide gel in the treatment of moderate to severe acne vulgaris

@#INTRODUCTION: Acne vulgaris has multifactorial causes. Prolonged systemic antibiotics are often necessary because relapse of lesions occurs upon its discontinuation. Currently, antimicrobial resistance is a growing concern. Androgen inhibitors like metformin may decrease need for antibiotics and maintain adequate control of the disease. OBJECTIVE: To determine the efficacy and safety of metformin versus placebo as an adjunct to lymecycline and adapalene+benzoyl peroxide gel in the treatment of moderate to severe acne vulgaris METHODS: Patients with moderate to severe acne vulgaris received either metformin or placebo tablets, together with lymecycline and adapalene+benzoyl peroxide gel. Lymecycline was taken for six weeks. The rest were given for 18 weeks. Evaluation was done biweekly using the mean reduction rates of non-inflammatory, inflammatory and total lesion count, modified global severity score, subjective self-assessment score, Dermatology life quality index (DLQI) score, and cutaneous and systemic adverse events. RESULTS: Forty patients were selected for the trial. Mean reduction rates of the non-inflammatory lesion counts of the two groups were comparable (p>0.05). Mean reduction rates of the inflammatory and total lesion count in the metformin group were higher than the placebo group (p<0.05). The mean modified global severity score of the metformin group was lower than the placebo group (p=0.034). Mean DLQI scores decreased in both groups (p<0.0001). Subjective self-assessment scores improved in both groups with comparable results. Cutaneous adverse events (erythema, pain, scaling, and dryness) were tolerable. Systemic adverse events (diarrhea, flatulence, headache, and epigastric pain) were self-limited CONCLUSION: Metformin is an effective and safe adjunct in the treatment of moderate to severe acne vulgaris.

Análisis retrospectivo del uso de la cuádruple terapia con bismuto (Pylera(R)) en la práctica clínica real en España / Retrospective analysis of the use of quadruple therapy with bismuth (Pylera(R)) in real-life clinical practice in Spain

OBJETIVO: La resistencia de Helicobacter pylori a los antibióticos es un problema creciente en nuestro medio y es necesario mejorar las tasas de erradicación. La cuádruple terapia con bismuto se ha considerado el tratamiento de primera o segunda línea en el nuevo consenso. Este estudio evalúa el uso de Pylera(R) en un escenario clínico real. PACIENTES Y MÉTODOS: Se llevó a cabo un estudio descriptivo transversal, entre marzo y septiembre de 2016, para evaluar los porcentajes de erradicación de Helicobacter pylori en pacientes tratados con Pylera(R). Los pacientes (naïve o con fallo a terapias previas) fueron tratados durante 10 días. La erradicación fue confirmada usando un test del aliento con urea al menos 30 días después de la finalización del tratamiento. Además se recogieron datos demográficos, clínico-analíticos y relacionados con el tratamiento. RESULTADOS: Fueron incluidos 185 pacientes (51,6±16,19 años); el 63,8% fueron mujeres y el 9,2% tenían historia familiar de cáncer gástrico. La indicación más frecuente fue la dispepsia (55,1%). El 57,8% recibieron Pylera(R) como primera línea de tratamiento. El 95,7% asociaron omeprazol. Se detectó una tasa de erradicación en primera línea de tratamiento del 78,15% por intención de tratar (86,6% por protocolo). No hubo diferencias estadísticamente significativas entre pacientes naïve y los tratados previamente. Nueve pacientes abandonaron el tratamiento (4,9%), 7 debido a efectos secundarios leves y 2 por toma incorrecta. CONCLUSIONES: Pylera(R) tiene unas aceptables tasas de erradicación como primera y segunda línea de tratamiento y muestra un adecuado perfil de seguridad

OBJECTIVE: The resistance of Helicobacter pylori to antibiotics is a growing problem in Spain and eradication rates must be improved. The new Spanish consensus considers quadruple therapy with bismuth as first- or second-line therapy. This study evaluated the use of Pylera(R) in real-life clinical practice. PATIENTS AND METHODS: A cross-sectional descriptive study was conducted to evaluate the eradication rate of Helicobacter pylori in patients treated with Pylera(R) between March and September 2016. Patients (naïve or with previous treatment failure) were treated for 10 days. Eradication was confirmed using a breath test with urea 30 days or more after treatment. In addition, demographic, clinical-analytical and treatment-related data were collected. RESULTS: A total of 185 patients were included (51.6±16.19 years); 63.8% were women and 9.2% had a family history of gastric cancer. The most frequent indication was dyspepsia (55.1%). Approximately 57.8% received Pylera(R) as first-line therapy, while 95.7% received Pylera(R) in combination with omeprazole. A first-line eradication rate of 78.15% was observed in the intention-to-treat population (86.6% per protocol). There were no statistically significant differences between naïve patients and those previously treated. Nine patients abandoned the treatment (4.9%), 7 due to mild side effects and 2 due to incorrect dosing. CONCLUSIONS: Pylera(R) has acceptable eradication rates in first- and second-line therapy and shows a suitable safety profile

Isotretinoin and lymecycline treatments modify the skin microbiota in acne.

Oral retinoids and tetracyclines have a major role in acne treatment. Here, we report for the first time the effect of isotretinoin and lymecycline therapy on the skin microbiota in cheek, back and armpit swab samples of acne vulgaris patients using 16S ribosomal RNA (16S rRNA) gene amplicon sequencing. Propionibacterium acnes was the most common in sebaceous areas of healthy and untreated acne skin and more abundant in back than cheek samples. Five taxa, including a Streptococcus taxon, differed significantly between the cheek samples of healthy controls and acne patients, and acne severity was positively correlated with the abundance of Propionibacterium. Both treatments reduced clinical acne grades and the abundance of Propionibacterium, while the abundance of several other taxa was significantly higher in treated cheek samples compared with untreated ones. Less variation was observed in back samples and none in armpit samples. There were no differences in alpha diversity between control and acne patients in any of the sampled skin areas, but the diversity of the microbiota on the cheek and the back was significantly increased after acne treatments. This study provides insight into the skin microbiota in acne and how it is modulated by systemic acne treatment.

Metformin as an adjunct therapy for the treatment of moderate to severe acne vulgaris.

The purpose of this literature review is to evaluate the use of metformin as an adjunct therapy in the treatment of moderate-to-severe acne in those not diagnosed with polycystic ovary syndrome (PCOS) or androgen excess. The authors conducted independent literature searches. Results were limited to clinical trials and randomized controlled trials. Studies with participants diagnosed with moderateto-severe acne vulgaris taking metformin versus placebo or other active treatment were included;studies with participants diagnosed with PCOS or androgen excess were excluded. The authors found three studies consistent with the search guidelines that evaluated the effects of metformin as adjunct therapy in moderate to severe acne vulgaris. In eachstudy, metformin was an effective adjunct therapy in the treatment of moderate-to-severe acne vulgaris.

Treatment of Mycobacterium marinum with lymecycline: new therapeutic alternative?

Skin infections by Mycobacterium marinum are quite rare in our environment and, therefore, little studied. The majority of the lesions appear three weeks after traumas in aquariums, beaches and fish tanks. Lymph node drainage and systematization of the disease are rare and most lesions disappear in about three years. This case aims to show the effectiveness of the treatment used (lymecycline 150 mg/orally/day). This medication may be a new therapeutic option for the treatment of Mycobacterium marinum.

Treatment of Mycobacterium marinum with lymecycline: new therapeutic alternative?

Skin infections by Mycobacterium marinum are quite rare in our environment and, therefore, little studied. The majority of the lesions appear three weeks after traumas in aquariums, beaches and fish tanks. Lymph node drainage and systematization of the disease are rare and most lesions disappear in about three years. This case aims to show the effectiveness of the treatment used (lymecycline 150 mg/orally/day). This medication may be a new therapeutic option for the treatment of Mycobacterium marinum.