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Annals of the Academy of Medicine,... Dec 2022The oral antiviral agents nirmatrelvir-ritonavir (NMV/r) and molnupiravir are used to treat mild-to-moderate COVID-19 infection in outpatients. However, the use of NMV/r...
INTRODUCTION
The oral antiviral agents nirmatrelvir-ritonavir (NMV/r) and molnupiravir are used to treat mild-to-moderate COVID-19 infection in outpatients. However, the use of NMV/r is complicated by significant drug-drug interactions (DDIs) with frequently prescribed medications. Healthcare professionals should be aware of the possible risk of DDIs, given the emergence of COVID-19 variants and the widespread use of oral COVID-19 treatments. We reviewed available data on DDIs between NMV/r, molnupiravir and common dermatological medications; summarised the potential side effects; and suggest strategies for safe COVID-19 treatment.
METHOD
A systematic review using PubMed was conducted on data published from inception to 18 July 2022 to find clinical outcomes of DDIs between NMV/r, molnupiravir and dermatological medications. We also searched the Lexicomp, Micromedex, Liverpool COVID-19 Drug Interactions database and the National Institutes of Health COVID-19 Treatment Guidelines for interactions between NMV/r and molnupiravir, and commonly used dermatological medications.
RESULTS
NMV/r containing the cytochrome P-450 (CYP) 3A4 inhibitor ritonavir has DDIs with other medications similarly dependent on CYP3A4 metabolism. Dermatological medications that have DDIs with NMV/r include rifampicin, clofazimine, clarithromycin, erythromycin, clindamycin, itraconazole, ketoconazole, fluconazole, bilastine, rupatadine, dutasteride, ciclosporin, cyclophosphamide, tofacitinib, upadacitinib, colchicine and systemic glucocorticoids. With no potential DDI identified yet in in vitro studies, molnupiravir may be an alternative COVID-19 therapy in patients taking medications that have complicated interactions with NMV/r, which cannot be stopped or dose adjusted.
CONCLUSION
NMV/r has significant DDIs with many common dermatological medications, which may require temporary discontinuation, dosage adjustment or substitution with other anti-COVID-19 agents such as molnupiravir.
Topics: Humans; Ritonavir; COVID-19; SARS-CoV-2; Antiviral Agents; Drug Interactions
PubMed: 36592146
DOI: 10.47102/annals-acadmedsg.2022289 -
Medical Archives (Sarajevo, Bosnia and... 2023The α-adrenergic receptor antagonist is the most effective medical therapy to reduce the dynamic component in patients with BPH. However, long-term administration of...
BACKGROUND
The α-adrenergic receptor antagonist is the most effective medical therapy to reduce the dynamic component in patients with BPH. However, long-term administration of receptor antagonists can cause upregulation of mRNA receptor expression, resulting in tolerance of drug effectiveness. PKC-α is involved in the process of prostate smooth muscle contraction through activation of the voltage-gated Ca2+ conducted canal, influenced by androgen hormones, especially testosterone, and has an isoform with Twist1, a transcription factor that plays a role in up-regulation of androgen receptors.
OBJECTIVE
The aim of the study was to compare the effect of long-term tamsulosin monotherapy and tamsulosin - dutasteride combination therapy in PKC-α enzyme expression in prostate stromal tissue of Rattus norvegicus rats of Wistar strain.
METHODS
Out of 80 samples of Rattus norvegicus rats were divided into 8 groups with different interventions: negative control group, positive control group, tamsulosin monotherapy administration for 1 day, 3 day, and 6 day groups, and tamsulosin - dutasteride combination therapy for 1 day, 3 day, and 6 day groups. BPH was induced with 3 mg/kg of testosterone proprionate for 3 weeks, continued with drugs administration according to intervention grouping. Prostate stromal tissue was taken and prepared for PKC-α enzyme measurement with ELISA method.
RESULTS
There was a significant difference (p<0.05) in the effect of tamsulosin monotherapy and tamsulosin-dutasteride combination therapy on the PKC-α expression. There was a strong positive relationship between the duration of tamsulosin-dutasteride combination therapy on the PKC-α expression, which means the longer the duration of the combination of tamsulosin-dutasteride combination the higher the PKC-α expression.
CONCLUSION
Administration of long-term tamsulosin - dutasteride combination therapy causes upregulation PKC-α expression more than tamsulosin only.
Topics: Animals; Male; Rats; 5-alpha Reductase Inhibitors; Azasteroids; Drug Therapy, Combination; Dutasteride; Prostate; Prostatic Hyperplasia; Rats, Wistar; Sulfonamides; Tamsulosin; Testosterone
PubMed: 38313112
DOI: 10.5455/medarh.2023.77.446-450 -
Archivio Italiano Di Urologia,... Dec 2022To the Editor, Benign prostatic hyperplasia (BPH) is a common cause of lower urinary tract symptoms (LUTS) in elderly males. The current guidelines recommend the use of...
To the Editor, Benign prostatic hyperplasia (BPH) is a common cause of lower urinary tract symptoms (LUTS) in elderly males. The current guidelines recommend the use of a 5-alpha reductase inhibitor (5ARI) to treat males with moderate-to-severe LUTS and an enlarged prostate. Combination therapy with an alpha blocker and a 5ARI has proven effective at ameliorating LUTS and reducing the total prostate volume (TPV) and the risk of the disease progression.
Topics: Male; Humans; Aged; Dutasteride; Prostatic Hyperplasia; 5-alpha Reductase Inhibitors; Adrenergic alpha-Antagonists; Prostate; Lower Urinary Tract Symptoms; Drug Therapy, Combination
PubMed: 36576460
DOI: 10.4081/aiua.2022.4.521 -
Prostate International Dec 2022To evaluate the short-term efficacy of Dutasteride in the management of chronic prostatitis (CP)/chronic pelvic pain syndrome.
OBJECTIVE
To evaluate the short-term efficacy of Dutasteride in the management of chronic prostatitis (CP)/chronic pelvic pain syndrome.
MATERIALS AND METHODS
A randomized placebo-controlled double-blind study was conducted that including 50 patients diagnosed with CP based on the presence of pelvic pain for ≥3 months of the preceding 6 months. Patients were randomized into 2 equal groups to evaluate Dutasteride of 0.5 mg once daily that was given for 3 months compared to a placebo.
RESULTS
Forty-nine patients were evaluated after the follow-up period with no statistically significant difference in the perioperative demographic data. The mean age of the Dutasteride group was 48.3 (range 41-62) compared to a mean age of 46.5 (range 44-60) in the placebo group. There was a highly statistically significant improvement in the Dutasteride group compared to its preoperative parameters and the placebo compared group in the terms of pain, urinary scores, and total National Institutes of Health CP symptom score. Moderate and marked improvement in patients' symptomatology was seen in 56% of the dutasteride group, while only 8% in the dutasteride group failed to show an improvement with no significant side effects noted in our study.
CONCLUSION
The short-term outcome of dutasteride therapy showed an improvement in the National Institutes of Health-CP symptom score compared to a placebo in the treatment of category IIIB CP.
THE TRIAL WAS REGISTERED IN THE CLINICAL TRIALGOV REGISTRY WITH A REGISTRATION NUMBER
NCT04756206.
PubMed: 36570649
DOI: 10.1016/j.prnil.2022.06.002 -
Prostate International Dec 2022Benign prostatic hyperplasia (BPH) refers to nonmalignant hyperplasia of prostate tissue, which causes lower urinary tract symptoms and has become a global public health...
OBJECTIVES
Benign prostatic hyperplasia (BPH) refers to nonmalignant hyperplasia of prostate tissue, which causes lower urinary tract symptoms and has become a global public health concern in the aging population. The purpose of this study is to identify modifiable factors, which would prevent or delay BPH development.
METHODS
The association between BPH marker drugs and climate-, socioeconomic-, health condition-, and lifestyle habits-related variables was investigated by analyzing nationwide datasets which were collected in 2018, aggregated by prefecture (administrative unit), and published by Japanese ministries. Uroselective α receptor blockers and dutasteride were used as marker drugs referring to BPH prevalence. Correlation analysis, multiple linear regression analysis, and binomial logistic regression analysis were conducted with 47 Japanese prefectures as the unit.
RESULTS
The variables which showed || > 0.5 by correlation analysis were exercise habits ( = -0.5696), smoking habits ( = 0.6116), and daily drinking ( = 0.6001) for uroselective α receptor blockers, and antihypertensive medication ( = 0.5971), smoking habits ( = 0.6598), a small amount of drinking ( = -0.5292), and serum alanine aminotransferase ( = 0.6814) for dutasteride. Multiple linear regression equations were constructed by including these variables ( = 0.5453 for uroselective α receptor blockers and = 0.5673 for dutasteride). Binomial logistic regression analysis found a significant association between climate in the resident area and BPH development.
CONCLUSION
This ecological study, analyzing Japanese nationwide datasets, demonstrates that healthy lifestyle habits, especially avoidance of smoking, implementation of exercise in daily life, and a small amount of alcohol consumption, are important to prevent or delay BPH development. High blood pressure and high serum alanine aminotransferase are suggested as risk factors of BPH development.
PubMed: 36570647
DOI: 10.1016/j.prnil.2022.06.004 -
Healthcare (Basel, Switzerland) Dec 2022Pharmacological treatment of benign prostatic hyperplasia (BPH)/benign prostatic obstruction (BPO)-associated lower urinary tract symptoms (LUTS) aims at improving...
BACKGROUND
Pharmacological treatment of benign prostatic hyperplasia (BPH)/benign prostatic obstruction (BPO)-associated lower urinary tract symptoms (LUTS) aims at improving patients' quality of life by managing urinary symptoms and preventing complications and disease progression. However, continuous use of drugs to treat BPH/BPO-associated LUTS decreases over time. The aim of this retrospective observational study was to describe use of α1-adrenoceptor antagonists (ABs) and steroid 5α-reductase inhibitors (5ARIs) by adult (age ≥ 40 years) men in the ASL TO4, a Local Health Authority in the northern area of the city of Turin (Italy).
METHODS
Persistence measures were adopted as a robust, informative, and feasible way to understand medication-taking behavior and to assess patient compliance.
RESULTS
A total of 4309 men (median age 71 years) were enrolled. Monotherapy was the treatment option prescribed to the largest part of the study population. However, ≥two drugs were prescribed to a substantial proportion of men (23%). Men prescribed alfuzosin or dutasteride had significantly greater persistence, which decreased over time.
CONCLUSIONS
Unmet needs and areas of intervention for healthcare systems aimed at improving the use of drugs for BHP/BPO-associated LUTS in the ASL TO4 Regione Piemonte were identified.
PubMed: 36554090
DOI: 10.3390/healthcare10122567 -
JAMA Network Open Dec 2022In recent decades, there has been increased interest in the possible adverse neurological effects of 5α-reductase inhibitors (5-ARIs), which have been used mainly for...
IMPORTANCE
In recent decades, there has been increased interest in the possible adverse neurological effects of 5α-reductase inhibitors (5-ARIs), which have been used mainly for benign prostatic hyperplasia and androgenic alopecia. Numerous studies and reports have indicated associations of 5-ARIs with depression and suicide. However, most of these studies had methodological shortcomings, and very little is known about the potential association of 5-ARIs with dementia.
OBJECTIVE
To investigate the association of 5-ARI use with all-cause dementia, Alzheimer disease, vascular dementia, depression, and suicide.
DESIGN, SETTING, AND PARTICIPANTS
This Swedish register-based cohort study included 2 236 876 men aged 50 to 90 years between July 1, 2005, and December 31, 2018. Statistical analyses were performed from September 15, 2021, to May 25, 2022.
MAIN OUTCOMES AND MEASURES
A diagnosis of all-cause dementia, Alzheimer disease, vascular dementia, depression, or completed suicide.
EXPOSURES
A recorded prescription in the Swedish national prescription register of finasteride or dutasteride and duration of use.
RESULTS
Of 2 236 876 men (median age at the start of follow-up, 55 years [IQR, 50-65 years] and at treatment initiation, 73 years [IQR, 66-80 years]), 70 645 (3.2%) started finasteride treatment, and 8774 (0.4%) started dutasteride treatment. Men taking finasteride or dutasteride were at increased risk of all-cause dementia (finasteride: hazard ratio [HR], 1.22 [95% CI, 1.17-1.28]; dutasteride: HR, 1.10 [95% CI, 1.01-1.20]), Alzheimer disease (finasteride: HR, 1.20 [95% CI, 1.10-1.31]; dutasteride: HR, 1.28 [95% CI, 1.09-1.50]), vascular dementia (finasteride: HR, 1.44 [95% CI, 1.30-1.58]; dutasteride: HR, 1.31 [95% CI, 1.08-1.59]), and depression (finasteride: HR, 1.61 [95% CI, 1.48-1.75]; dutasteride: HR, 1.68 [95% CI, 1.43-1.96]). However, the magnitude of the association decreased over time, and the findings became statistically nonsignificant with continuous exposures over 4 years, except for depression, which showed a constant risk over time, with no differences between finasteride and dutasteride. In contrast, 5-ARIs were not associated with suicide (finasteride: HR, 1.22 [95% CI, 0.99-1.49]; dutasteride: HR, 0.98 [95% CI, 0.62-1.54]).
CONCLUSIONS AND RELEVANCE
This cohort study found that, while men receiving 5-ARI treatment showed a higher risk for dementia in the initial periods after starting treatment, the decreasing magnitude of the association over time suggested that the risk may be, entirely or in part, due to increased dementia detection among patients with benign prostate enlargement. Both finasteride and dutasteride were similarly associated with depression with a constant risk over time, while neither drug was associated with suicide. Prescribing clinicians and potential users should be aware of the possible risks for depression associated with 5-ARI use.
Topics: Humans; Male; 5-alpha Reductase Inhibitors; Alzheimer Disease; Cohort Studies; Dementia, Vascular; Depression; Dutasteride; Finasteride; Prostatic Hyperplasia; Retrospective Studies; Suicide; Antineoplastic Agents
PubMed: 36547981
DOI: 10.1001/jamanetworkopen.2022.48135 -
Scientific Reports Dec 2022Caffeic acid derivatives containing amide moieties similar to those of finasteride and dutasteride were synthesized. An in vitro inhibitory activity evaluation of...
Caffeic acid N-[3,5-bis(trifluoromethyl)phenyl] amide as a non-steroidal inhibitor for steroid 5α-reductase type 1 using a human keratinocyte cell-based assay and molecular dynamics.
Caffeic acid derivatives containing amide moieties similar to those of finasteride and dutasteride were synthesized. An in vitro inhibitory activity evaluation of caffeic acid (1) and its amide derivatives (2 - 4) against the steroid 5α-reductase type 1 (SRD5A1) produced by human keratinocyte cells coupled with the non-radioactive high-performance thin-layer chromatography detection revealed that caffeic acid N-[3,5-bis(trifluoromethyl)phenyl] amide (4) was a promising non-steroidal suppressor, with a half-maximal inhibitory concentration (IC) of 1.44 ± 0.13 µM and relatively low cytotoxicity with an IC of 29.99 ± 8.69 µM. The regulatory role of compound 4 against SRD5A1 involved both suppression of SRD5A1 expression and mixed mode SRD5A1 inhibition. The K value of compound 4 was 2.382 µM based on the whole-cell kinetic studies under specific conditions. Molecular docking and molecular dynamics simulations with AlphaFold generated the human SRD5A1 structure and confirmed the stability of compound 4 at the SRD5A1 catalytic site with greater interactions, including hydrogen bonding of the key M119 amino-acid residue than those of finasteride and dutasteride. Thus, compound 4 shows the potential for further development as an SRD5A1 suppressor for androgenic alopecia treatment.
Topics: Humans; Molecular Dynamics Simulation; Amides; Molecular Docking Simulation; Finasteride; Dutasteride; Kinetics; Keratinocytes
PubMed: 36460729
DOI: 10.1038/s41598-022-25335-7 -
Frontiers in Bioengineering and... 2022Androgenic alopecia (AGA) is a common disease that negatively affects patients' physical and mental health. AGA can be treated with drugs that improve the perifollicular...
Androgenic alopecia (AGA) is a common disease that negatively affects patients' physical and mental health. AGA can be treated with drugs that improve the perifollicular microenvironment, such as 5α-reductase inhibitors (e.g., dutasteride [DUT]), androgen receptor blockers, and minoxidil. However, the efficacy of these treatments is limited. Therefore, this study aimed to show that nanoparticles are effective as stable carriers with high curative benefits and little adverse effects. The study showed that PLGA-DUT/siAR@DPCM NPs could deliver both DUT and siAR to dermal papilla cells. They could successfully suppress 5α-reductase and knock down androgen receptor, respectively, and thereby promote cell proliferation. In the study, PLGA-DUT/siAR@DPCM NPs showed a significant therapeutic effect in an AGA mouse model. They successfully penetrated the stratum corneum and showed a clear targeting effect on hair follicles and surrounding tissues. PLGA-DUT/siAR@DPCM NPs could enable the targeted delivery of DUT and siAR through percutaneous penetration, enhancing phagocytosis and decreasing adverse effects. Thus, they have great potential in the clinical treatment of AGA.
PubMed: 36394031
DOI: 10.3389/fbioe.2022.1033987 -
Medicine Nov 2022We performed a retrospective study to clarify the characteristics of prostate biopsies in patients treated with dutasteride, a benign prostate hyperplasia treatment drug...
We performed a retrospective study to clarify the characteristics of prostate biopsies in patients treated with dutasteride, a benign prostate hyperplasia treatment drug that inhibits 5α-reductase. We studied the digital clinical data of 677 patients, including 96 cases treated with dutasteride, with suspected localized prostate cancer. All patients underwent transrectal ultrasonography-guided prostate biopsy between 2014 and 2017 in our department. A propensity score matching analysis was performed based on prostate-specific antigen (PSA) (calculated as double the PSA value for the dutasteride group) and age. Ninety-six patients in each of the dutasteride and control groups were assessed and their characteristics were compared. The characteristics of the patients in the dutasteride and control groups were well balanced by matching. There were fewer prostate cancer-positive patients in the dutasteride group. When comparing only the prostate cancer-positive patients in each group, there were significantly more cases of high-grade cancers and abnormal magnetic resonance imaging (MRI) findings in the dutasteride group. In the dutasteride group, abnormal MRI findings and advanced age were significant predictors of high grade cancer. This study shows the characteristics of prostate biopsies in patients treated with dutasteride and indicates that patients on dutasteride with advanced age and abnormal MRI findings should undergo prostate biopsy.
Topics: Male; Humans; Dutasteride; Prostate; Prostate-Specific Antigen; Azasteroids; 5-alpha Reductase Inhibitors; Retrospective Studies; Biopsy; Prostatic Neoplasms
PubMed: 36343082
DOI: 10.1097/MD.0000000000031658