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Genes Jul 2021Hydroxyurea (HU) is mostly referred to as an inhibitor of ribonucleotide reductase (RNR) and as the agent that is commonly used to arrest cells in the S-phase of the... (Review)
Review
Hydroxyurea (HU) is mostly referred to as an inhibitor of ribonucleotide reductase (RNR) and as the agent that is commonly used to arrest cells in the S-phase of the cycle by inducing replication stress. It is a well-known and widely used drug, one which has proved to be effective in treating chronic myeloproliferative disorders and which is considered a staple agent in sickle anemia therapy and-recently-a promising factor in preventing cognitive decline in Alzheimer's disease. The reversibility of HU-induced replication inhibition also makes it a common laboratory ingredient used to synchronize cell cycles. On the other hand, prolonged treatment or higher dosage of hydroxyurea causes cell death due to accumulation of DNA damage and oxidative stress. Hydroxyurea treatments are also still far from perfect and it has been suggested that it facilitates skin cancer progression. Also, recent studies have shown that hydroxyurea may affect a larger number of enzymes due to its less specific interaction mechanism, which may contribute to further as-yet unspecified factors affecting cell response. In this review, we examine the actual state of knowledge about hydroxyurea and the mechanisms behind its cytotoxic effects. The practical applications of the recent findings may prove to enhance the already existing use of the drug in new and promising ways.
Topics: Animals; DNA Replication; Humans; Hydroxyurea; Ribonucleotide Reductases; S Phase
PubMed: 34356112
DOI: 10.3390/genes12071096 -
Expert Opinion on Drug Safety 2015Sickle cell anemia (SCA) is a severe, inherited hemoglobin disorder affecting 100,000 persons in the US and millions worldwide. Hydroxyurea, a once daily oral... (Review)
Review
INTRODUCTION
Sickle cell anemia (SCA) is a severe, inherited hemoglobin disorder affecting 100,000 persons in the US and millions worldwide. Hydroxyurea, a once daily oral medication, has emerged as the primary disease-modifying therapy for SCA. The accumulated body of evidence over 30 years demonstrates that hydroxyurea is a safe and effective therapy for SCA, but hydroxyurea remains underutilized for a variety of reasons.
AREAS COVERED
In this review, we summarize the available evidence regarding the pharmacology, clinical, and laboratory benefits, and safety of hydroxyurea therapy for the treatment of SCA. The purpose of this review is to provide the reader a comprehensive understanding of hydroxyurea and to reinforce the fact that hydroxyurea is a safe and effective medication for the treatment of SCA.
EXPERT OPINION
In our opinion, hydroxyurea therapy should be considered standard-of-care for SCA, representing an essential component of patient management. Early initiation and broader use of hydroxyurea will alter the natural history of SCA, so affected children can live longer and healthier lives. In addition, hydroxyurea use should be extended to low-resource settings such as sub-Saharan Africa, where the burden of SCA and the need for hydroxyurea is arguably the greatest.
Topics: Administration, Oral; Anemia, Sickle Cell; Animals; Antisickling Agents; Humans; Hydroxyurea
PubMed: 26366626
DOI: 10.1517/14740338.2015.1088827 -
Revista Medica de Chile Sep 2021Sickle cell anemia is a type of hemoglobinopathy characterized by a specific mutation in the beta globin gene with the consequent generation of an unstable hemoglobin...
Sickle cell anemia is a type of hemoglobinopathy characterized by a specific mutation in the beta globin gene with the consequent generation of an unstable hemoglobin that crystallizes in a state of hypoxia. This causes a change in the structure of the red blood cell, which ends up producing vaso-occlusion with the corresponding clinical complications for the patient. Worldwide, various diagnostic tests have been developed that allow the appropriate approach to the affected patient. These include techniques for the determination of hemoglobin and the use of molecular markers, among others. There are new therapeutic alternatives to the use of hydroxyurea and L-glutamine, such as the use of gene therapy tools. The most recent experimental trials are exploring gene editing techniques.
Topics: Anemia, Sickle Cell; Haplotypes; Humans; Hydroxyurea; Hypoxia
PubMed: 35319686
DOI: 10.4067/S0034-98872021000901322 -
BMJ Clinical Evidence Jan 2016Sickle cell disease causes chronic haemolytic anaemia, dactylitis, and painful acute crises. It also increases the risk of stroke, organ damage, bacterial infections,... (Review)
Review
INTRODUCTION
Sickle cell disease causes chronic haemolytic anaemia, dactylitis, and painful acute crises. It also increases the risk of stroke, organ damage, bacterial infections, and complications of blood transfusion. In sub-Saharan Africa, up to one third of adults are carriers of the defective sickle cell gene, and 1% to 2% of babies are born with the disease.
METHODS AND OUTCOMES
We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of pharmaceutical interventions to prevent sickle cell crisis and other acute complications in people with sickle cell disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2015 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).
RESULTS
At this update, searching of electronic databases retrieved 369 studies. After deduplication and removal of conference abstracts, 136 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 99 studies and the further review of 37 full publications. Of the 37 full articles evaluated, three already included systematic reviews were updated, two systematic reviews, two RCTs, and one subsequent RCT were added at this update. We performed a GRADE evaluation for 12 PICO combinations.
CONCLUSIONS
In this systematic overview, we categorised the efficacy for five interventions based on information about the effectiveness and safety of antibiotic prophylaxis in children aged under 5 years, antibiotic prophylaxis in children aged 5 years or older, hydroxyurea, malaria chemoprophylaxis, and pneumococcal vaccines.
Topics: Anemia, Sickle Cell; Antibiotic Prophylaxis; Blood Transfusion; Humans; Hydroxyurea; Pneumococcal Vaccines
PubMed: 26808098
DOI: No ID Found -
Comptes Rendus Biologies Mar 2013Due to its oral route of administration and mild toxicity profile, as well as its potent laboratory and clinical effects, hydroxyurea (or hydroxycarbamide) has been the... (Review)
Review
Due to its oral route of administration and mild toxicity profile, as well as its potent laboratory and clinical effects, hydroxyurea (or hydroxycarbamide) has been the primary focus of fetal hemoglobin (HbF) induction strategies for the treatment of children with sickle cell anemia (SCA). When administered orally once a day, hydroxyurea treatment is very well tolerated with little short-term toxicity. Hydroxyurea has documented laboratory efficacy with increases in Hb and HbF; treatment also significantly reduces the number of painful episodes, acute chest syndrome, transfusions, and hospitalizations. Most young patients reach a maximum tolerated dose of hydroxyurea at 25-30 mg/kg/d, where they will achieve key laboratory thresholds (Hb ≥ 9 g/dL and HbF ≥ 20%) without excessive myelosuppression. Potential long-term toxicities continue to be of great concern and should be monitored in all patients with SCA who receive hydroxyurea therapy. To date, however, no increases in stroke, myelodysplasia, or carcinogenicity have been detected in SCA patient cohorts, with drug exposure now reaching 15 years for some treated children. Taken together, available evidence suggests that hydroxyurea represents an inexpensive and effective treatment option that should be offered to most, if not all, patients with SCA. As countries in Africa develop newborn screening programs to identify SCA, the widespread use of hydroxyurea may prove to be a useful treatment to help ameliorate the disease in resource-limited settings. Hydroxyurea is the only currently available disease-modifying therapy for SCA, and is emerging as a safe and effective treatment for all patients with SCA, in both developed and developing countries.
Topics: Agranulocytosis; Anemia, Sickle Cell; Antisickling Agents; Clinical Trials as Topic; Developing Countries; Forecasting; Gastrointestinal Diseases; Humans; Hydroxyurea; Hyperpigmentation; Maximum Tolerated Dose; Multicenter Studies as Topic; Treatment Outcome
PubMed: 23643402
DOI: 10.1016/j.crvi.2012.09.006 -
Blood Feb 2021
Topics: Anemia, Sickle Cell; Humans; Hydroxyurea
PubMed: 33570614
DOI: 10.1182/blood.2020010033 -
Orphanet Journal of Rare Diseases Mar 2021Hydroxyurea and blood transfusion therapies remain the main therapeutic strategies for Sickle cell disease. Preliminary data suggest substantial variation and... (Review)
Review
BACKGROUND
Hydroxyurea and blood transfusion therapies remain the main therapeutic strategies for Sickle cell disease. Preliminary data suggest substantial variation and inconsistencies in practice of these two therapeutic modalities in South Asia. In this systematic review we searched Medline, Cochrane library and Scopus for articles on usage of hydroxyurea and blood transfusion therapies for sickle cell disease in South Asia published in English between October 2005 and October 2020.
RESULTS
We selected 41 papers: 33 from India, 3 from Sri Lanka, 2 each from Pakistan and Bangladesh and one from Nepal. Only 14 prospective trials focused on hydroxyurea therapy from which majority (n = 10; 71.4%) adopted fixed low dose (10 mg/kg/day) regimen. With hydroxyurea therapy, 12 and 9 studies reported significant reductions in vaso-occlusive crises and transfusion requirement respectively. Severe anaemia (haemoglobin level < 6-7 g/dl) was the commonest indicator (n = 8) for transfusion therapy followed by vaso-occlusive crisis.
CONCLUSIONS
Published data on the hydroxyurea and transfusion therapies in South Asia are limited and heterogeneous. A clear gap of knowledge exists about the nature of the sickle cell disease in the Indian subcontinent particularly from countries outside India necessitating further evidence-based assessments and interventions.
Topics: Anemia, Sickle Cell; Bangladesh; Blood Transfusion; Humans; Hydroxyurea; India; Neglected Diseases; Pakistan; Prospective Studies
PubMed: 33757549
DOI: 10.1186/s13023-021-01781-w -
BMJ Case Reports Mar 2022
Topics: Humans; Hydroxyurea; Hyperpigmentation; Nails
PubMed: 35292553
DOI: 10.1136/bcr-2022-249123 -
Blood Feb 2021
Topics: Anemia, Sickle Cell; Antisickling Agents; Humans; Hydroxyurea; Male; Puberty; Spermatozoa
PubMed: 33570610
DOI: 10.1182/blood.2020008803 -
Current Opinion in Hematology May 2011Sickle cell anemia (SCA) is a well characterized severe hematological disorder with substantial morbidity and early mortality. Hydroxyurea is a potent inducer of fetal... (Review)
Review
PURPOSE OF REVIEW
Sickle cell anemia (SCA) is a well characterized severe hematological disorder with substantial morbidity and early mortality. Hydroxyurea is a potent inducer of fetal hemoglobin, and evidence over the past 25 years has documented its laboratory and clinical efficacy for both adults and children with SCA.
RECENT FINDINGS
The phase III study of hydroxyurea in infants (BABY HUG) has just been completed and preliminary results indicate equivocal benefits for organ protection during the 2-year treatment period, but significant benefits for pain, acute chest syndrome, hospitalizations, and transfusions. Three new reports document the benefits of hydroxyurea on reducing mortality in SCA: two adult trials (LaSHS and MSH) and one pediatric study (Brazilian cohort). Recent results from the HUSTLE protocol suggest minimal genotoxicity or carcinogenicity with long-term hydroxyurea exposure.
SUMMARY
The potential utility of hydroxyurea for all patients with SCA is clear and indisputable. With decades of accumulated evidence and documented efficacy with an acceptable long-term safety profile, it is time to consider hydroxyurea treatment the standard of care for all young patients with SCA. Exporting our knowledge and experience with hydroxyurea to developing nations with large medical burdens from SCA can help relieve global suffering from this condition.
Topics: Anemia, Sickle Cell; Humans; Hydroxyurea
PubMed: 21372708
DOI: 10.1097/MOH.0b013e32834521dd