Gynekomastie je benigní zvětšení prsní žlázy u mužů, které může mít významný psychologický dopad, zejména u dětí a adolescentů. Tento článek se zabývá farmakologicky indukovanou gynekomastií a nejčastějšími léky, které mohou přispět k jejímu vzniku. V rámci naší analýzy jsme identifikovali a přezkoumali relevantní studie a kazuistiky publikované v databázi PubMed, které se zabývají různými aspekty gynekomastie u dětských pacientů. Důležitým krokem v prevenci gynekomastie je informovanost zdravotnického personálu, rodičů a pacientů o potenciálních rizicích spojených s užíváním určitých léků. Je nevyhnutelné, aby při předepisovaní léčby byly zohledněny veškeré možné vedlejší účinky, a aby se provedlo důkladné zhodnocení poměru přínosů a rizik. Mimo jiné se doporučuje provádět pravidelné kontroly a hodnocení pacientů, kteří užívají rizikové léky, aby bylo možné včas identifikovat a řešit případné příznaky gynekomastie. Tento článek zdůrazňuje potřebu zvýšené pozornosti k vybraným lékům, které jsou nejčastěji uváděny v odborné literatuře, a multidisciplinární přístup k léčbě. Informovanost o farmakologických rizicích a podpora ze strany zdravotnických odborníků jsou klíčové pro prevenci a zvládnutí tohoto stavu, ale také pro psychologickou pohodu dětských pacientů trpících touto diagnózou.

Gynecomastia is a benign enlargement of breast tissue in males that can have significant psychological impacts, especially in children and adolescents. This article focuses on pharmacologically induced gynecomastia and the most common medications that may contribute to its development. In our analysis, we identified and examined relevant studies and case reports published in the PubMed database that discuss various aspects of gynecomastia in pediatric patients. An important step in the prevention of gynecomastia is the awareness of healthcare professionals, parents, and patients regarding the potential risks associated with the use of certain medications. It is essential that all possible side effects are considered when prescribing treatment and that a thorough assessment of the benefits and risks is conducted. Additionally, it is recommended to carry out regular check-ups and evaluations of patients who are taking high-risk medications to identify and address any symptoms of gynecomastia in a timely manner. This article emphasizes the need for increased attention to selected medications commonly cited in the scientific literature and a multidisciplinary approach to treatment. Awareness of pharmacological risks and support from healthcare professionals are crucial for the prevention and management of this condition, as well as for the psychological well-being of pediatric patients suffering from this diagnosis.

• MeSH
• Anticonvulsants pharmacology   adverse effects   MeSH
• Antipsychotic Agents pharmacology   adverse effects   MeSH
• Child MeSH
• Gynecomastia * etiology   MeSH
• Isoniazid pharmacology   adverse effects   MeSH
• Humans MeSH
• Metoclopramide pharmacology   adverse effects   MeSH
• Drug-Related Side Effects and Adverse Reactions * drug therapy   MeSH
• Omeprazole pharmacology   adverse effects   MeSH
• Check Tag
• Child MeSH
• Humans MeSH

Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .

• MeSH
• Anti-Bacterial Agents therapeutic use   administration & dosage   MeSH
• Adult MeSH
• Helicobacter pylori * drug effects   MeSH
• Helicobacter Infections * drug therapy   epidemiology   microbiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Metronidazole therapeutic use   administration & dosage   MeSH
• Stomach Neoplasms * prevention & control   epidemiology   microbiology   MeSH
• Omeprazole * therapeutic use   administration & dosage   MeSH
• Organometallic Compounds therapeutic use   administration & dosage   MeSH
• Aged MeSH
• Tetracycline therapeutic use   administration & dosage   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH
• Geographicals
• China MeSH

Background and Objectives: The enteric form of omeprazole is one of the most commonly prescribed medications. Similarly to Europe, Kazakhstan relies on the localization of pharmaceutical drug production as one of its primary strategies to ensure that its population has access to affordable and good-quality medicines. This study comprehensively describes the technologically available development of bioequivalent delayed-release omeprazole. Materials and Methods: Various regimes and technological parameters were tested on laboratory- and production-scale equipment to establish a technical process where a functional and gastro-protective layer is essential. According to the ICH guidance on stability testing and Kazakhstan local rules, stability studies were conducted under conditions appropriate for climate zone II. The comparison of the rate and extent of absorption with subsequent assessment of the bioequivalence of the generic and reference drugs after a single dose of each drug at a dose of 40 mg was performed. Results: The quantitative and qualitative composition and technology of producing a new generic enteric form of omeprazole in capsules were developed and implemented at the manufacturing site of solid forms. Dissolution profiles in media with pH 1.2 and 6.8 were proven. During the accelerated six-month and long-term twelve-month studies, the developed formulation in both packaging materials at each control point passed the average weight and mass uniformity test, dissolution test, acid-resistance stage test, buffer stage test, impurity assay, and microbiological purity test and met all the specification criteria. A bioequivalence study in 24 healthy volunteers compared against the innovative drug showed the bioequivalency of the new generic system. The obtained values from the test and reference products were 1321 ± 249.0 ng/mL and 1274 ± 233 ng/mL for Cmax, 4521 ± 841 ng·h /mL and 4371 ± 695 ng·h /mL for AUC0-t, and 4636 ± 814 ng·h /mL and 4502 ± 640 ng·h /mL for AUC0-∞. Conclusions: Using affordable technologies, a bioequivalent generic delayed-release formulation of 20 and 40 mg omeprazole has been developed.

• MeSH
• Cross-Over Studies MeSH
• Humans MeSH
• Omeprazole * chemistry   MeSH
• Therapeutic Equivalency MeSH
• Capsules MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe MeSH

Dasatinib monohydrate indicated for the treatment of chronic myeloid leukemia displays pH-dependent solubility. The aim of reported development program of novel dasatinib anhydrate containing formulation was to demonstrate improved absorption and lower pharmacokinetic variability compared to dasatinib monohydrate. In a bioavailability study comparing formulations containing 110.6 mg and 140 mg of dasatinib as anhydrate and monohydrate, respectively, both Cmax and AUC of dasatinib were within standard 80.00-125.00% range, while the intra- and inter-subject variability for AUC0-inf after the test product was approximately 3-fold and 1.5-fold less than after the reference, respectively.In a drug-drug interaction study, omeprazole 40 mg reduced the mean AUC0-inf of dasatinib by 19%, when the test was ingested 2 h before the 5th omeprazole dose. This decrease of exposure is clinically irrelevant and substantially less than after the reference. Co-prescription analysis supports the importance of pH-dependent solubility of dasatinib, as >21% of patients were treated concomitantly with a PPI and dasatinib despite warnings against this co-medication in the SmPC.The novel dasatinib anhydrate containing formulation demonstrated improved absorption and less pharmacokinetic variability compared to dasatinib monohydrate product, which may translate into improved clinical outcomes, although this needs to be proven by an appropriate trial.

• MeSH
• Administration, Oral MeSH
• Biological Availability MeSH
• Dasatinib MeSH
• Cross-Over Studies MeSH
• Humans MeSH
• Omeprazole * pharmacokinetics   MeSH
• Area Under Curve MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Proton-pump inhibitors (PPIs) are cornerstone treatments for gastro-esophageal reflux disease (GERD); however, evidence suggests that most patients exhibit partial response to PPIs, suggesting the need for novel therapies that can provide an improved and sustained increase in gastric pH. AIMS: This study aimed to determine the effect of vonoprazan, a novel, orally active small-molecule potassium-competitive acid blocker, versus esomeprazole, a PPI, in preventing heartburn symptoms over a 4-week treatment period in patients with GERD and a partial response to esomeprazole treatment. METHODS: This randomized, double-blind, proof-of-concept, phase 2 clinical trial was conducted between 2016 and 2018 at 39 sites across Europe and designed to evaluate the efficacy and safety of vonoprazan 20 mg once daily (q.d.) and 40 mg q.d. versus esomeprazole 40 mg q.d. after 1:1:1 randomization of symptomatic patients with GERD and a partial response to a healing dose of esomeprazole. RESULTS: Overall, 256 eligible patients (female, 59.4%; mean age, 52.6 years) received vonoprazan 20 mg (n = 85), vonoprazan 40 mg (n = 85), or esomeprazole 40 mg (n = 86); mean (SD) percentages of heartburn-free 24-h periods during double-blind treatment were 36.7% (33.4%), 36.5% (35.6%), and 38.4% (34.8%), respectively, with no intergroup statistical significance. Vonoprazan exposure increased proportionally from the 20-mg to 40-mg dose (mean Cmax : 23.3 ng/ml to 47.1 ng/ml, respectively). Most treatment-emergent adverse events were mild, with no deaths reported. CONCLUSIONS: No statistically significant difference in efficacy and safety was observed among treatment groups, and vonoprazan was well tolerated. The trial is registered with the National Board of Health (EudraCT: 2015-001154-14) database.

• MeSH
• Double-Blind Method MeSH
• Esomeprazole * therapeutic use   MeSH
• Gastroesophageal Reflux * drug therapy   diagnosis   MeSH
• Proton Pump Inhibitors therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Heartburn drug therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH

ACT-1014-6470 is an orally available complement factor 5a receptor 1 antagonist and a novel treatment option in auto-inflammatory diseases. The in vitro inhibition potential of ACT-1014-6470 on cytochrome P450 isozymes (CYPs) and its effect on the pharmacokinetics (PK) of the CYP2C19 and CYP3A4 substrates omeprazole and midazolam, respectively, in humans were assessed. In vitro assays were conducted with isoform-specific substrates in human liver microsomes. In an open-label, two-period, fixed-sequence cocktail study, single doses of 20 mg omeprazole and 2 mg midazolam were administered concomitantly to 20 healthy male subjects alone (treatment A) and after a single dose of 100 mg ACT-1014-6470 (treatment B) under fed conditions. Safety and PK assessments were performed. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of noncompartmental PK parameters of treatment B versus treatment A were calculated. In vitro, no time-dependent inhibition was observed and the lowest inhibition constant of 4.3 μM ACT-1014-6470 was recorded for CYP2C19. In humans, GMRs (90% CI) of omeprazole PK were 1.9 (1.5-2.5) for maximum plasma concentration (Cmax ) and 1.9 (1.5-2.3) for area under the plasma concentration-time curve from 0 to 12 h (AUC0-12 h ). Midazolam PK showed GMRs (90% CI) of 1.1 (1.1-1.2) for Cmax and 1.5 (1.4-1.6) for AUC0-24 h . All treatments were well-tolerated. In line with in vitro results and regulatory risk factor calculation, the increased exposure to omeprazole and midazolam in humans after concomitant administration with a single dose of 100 mg ACT-1014-6470 reflected a weak inhibition of CYP2C19 and CYP3A4.

• MeSH
• Cytochrome P-450 CYP3A * MeSH
• Cytochrome P-450 CYP2C19 MeSH
• Factor Va * MeSH
• Drug Interactions MeSH
• Humans MeSH
• Midazolam pharmacokinetics   MeSH
• Omeprazole pharmacokinetics   MeSH
• Cytochrome P-450 Enzyme System MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Proton pump inhibitors, such as omeprazole, pantoprazole and lansoprazole, are an important group of clinically used drugs. Generally, they are considered safe without direct toxicity. Nevertheless, their long-term use can be associated with a higher risk of some serious pathological states (e.g. amnesia and oncological and neurodegenerative states). It is well known that dysregulation of the metabolism of transition metals (especially iron ions) plays a significant role in these pathological states and that the above drugs can form complexes with metal ions. However, to the best of our knowledge, this phenomenon has not yet been described in water systems. Therefore, we studied the interaction between these drugs and transition metal ions in the surrounding water environment (water/DMSO, 99:1, v/v) by absorption spectroscopy. In the presence of Fe(III), a strong redshift was observed, and more importantly, the affinities of the drugs (represented as binding constants) were strong enough, especially in the case of omeprazole, so that the formation of a metallocomplex cannot be excluded during the explanation of their side effects.

• MeSH
• Proton Pump Inhibitors chemistry   MeSH
• Coordination Complexes chemistry   MeSH
• Lansoprazole * chemistry   MeSH
• Omeprazole chemistry   MeSH
• Pantoprazole chemistry   MeSH
• Transition Elements chemistry   MeSH
• Spectrophotometry * MeSH
• Water chemistry   MeSH
• Ferric Compounds chemistry   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Antipsychotic Agents therapeutic use   MeSH
• Administration, Oral MeSH
• Depressive Disorder * drug therapy   complications   MeSH
• Adult MeSH
• Hepatolenticular Degeneration * diagnosis   drug therapy   complications   MeSH
• Hepatic Insufficiency complications   MeSH
• Humans MeSH
• Lithium therapeutic use   MeSH
• Omeprazole administration & dosage   MeSH
• Penicillamine administration & dosage   therapeutic use   MeSH
• Deglutition Disorders complications   MeSH
• Selegiline therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

Autoři popisují případ 72leté nemocné s generalizovanými splývajícími anulárními projevy, které vznikly dva měsíce po zahájení léčby omeprazolem. Kožní biopsie z projevu prokázala "interface" dermatitidu slučitelnou s diagnózou léky indukovaného lupus erythematosus. Krátká kúra léčby prednisonem v dávce 60 mg/den a vysazení omeprazolu vedlo k ústupu projevů. Autoři předkládají současné poznatky o formách léky indukovaného lupus erythematosus.

The authors describe the case of a 72-year-old patient with generalized merging annular manifestations that occurred two months after the start of omeprazole treatment. The histologic examination confirmed "interface" dermatitis compatible with the diagnosis of drug induced lupus erythematosus. Short course of 60 mg prednison a day and discontinuation of omeprazol led to the regression of skin manifestations. The authors present current knowledge of drug induced lupus erythematosus forms.

• MeSH
• Lupus Erythematosus, Cutaneous * chemically induced   diagnosis   therapy   MeSH
• Humans MeSH
• Drug-Related Side Effects and Adverse Reactions MeSH
• Omeprazole * adverse effects   MeSH
• Prednisone administration & dosage   therapeutic use   MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

BACKGROUND: The aim of this study was comparison the effectiveness of sequential and standard quadruple therapy on eradication of H. pylori infection. METHODS: This clinical trial study was conducted on 160 patients with dyspepsia or gastroduodenal ulcer. Patients were randomly divided into two groups. Group A (standard regimen) received omeprazole, amoxicillin, clarithromycin and bismuth subcitrate for 2 weeks. Group B (sequential regimen) received omeprazole and amoxicillin in 5 days and omeprazole, tinidazole and levofloxacin in 5 days. After the end of treatment regimens, 20 mg omeprazole was administered twice daily for 3 weeks. H. pylori eradication was assessed 2 months after antibiotic treatment via fecal antigen. RESULTS: Frequency of H. pylori eradication in group A and B was observed in 55 (68.8%) and 63 patients (78.8%), respectively. No significant difference was seen between two groups, regarding H. pylori eradication (p = 0.15). The most common side effects in group A, B were bitterness of mouth (63.8%) and nausea (16.2%), respectively (p H. pylori infection, higher rate of H. pylori eradication was seen in group B than group A. Thus, sequential regimen was a more appropriate regimen with fewer complications.

• MeSH
• Amoxicillin administration & dosage   MeSH
• Adult MeSH
• Helicobacter pylori MeSH
• Helicobacter Infections drug therapy   MeSH
• Clarithromycin administration & dosage   MeSH
• Drug Therapy, Combination MeSH
• Levofloxacin administration & dosage   MeSH
• Middle Aged MeSH
• Humans MeSH
• Omeprazole administration & dosage   MeSH
• Organometallic Compounds administration & dosage   MeSH
• Aged MeSH
• Tinidazole administration & dosage   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial MeSH
• Comparative Study MeSH