sulfasalazine
Regulatory sources consulted
Approved indications
- Mild to moderate ulcerative colitis and adjunctive therapy in severe disease; the label also indicates prolonging the time between exacerbations.
Contraindications
Absolute
- Intestinal or urinary obstruction; porphyria; and hypersensitivity to sulfasalazine, its metabolites, sulfonamides, or salicylates.
Clinical warnings
- Major warning · It can cause serious hepatic, renal, or hematologic toxicity. Blood count and urinalysis monitoring are required; stop and assess if compatible signs occur. — DailyMed/FDA label
- Major warning · It may cause systemic hypersensitivity reactions and severe cutaneous adverse reactions, including DRESS, SJS/TEN, and AGEP. Discontinue at the first signs of hypersensitivity or severe skin reaction. — DailyMed/FDA label
- Major warning · Monitor for signs of serious infection; discontinue if a serious infection develops. Oligospermia and infertility observed in men appear reversible after withdrawal. — DailyMed/FDA label
Drug interactions
- ModerateFolic acid
Mechanism: It may reduce folic acid absorption.
Recommendation: Assess folate status and need for supplementation under clinical supervision.
DailyMed/FDA label
- ModerateDigoxin
Mechanism: It may reduce digoxin absorption.
Recommendation: Monitor clinical response and consider concentration monitoring according to the clinical situation.
DailyMed/FDA label
Adverse events
Common (≥1%)
Anorexia · headache · nausea · vomiting · gastric distress · reversible oligospermia
Rare but serious
Agranulocytosis · aplastic anemia · hepatitis or hepatic failure · nephritis · DRESS · SJS/TEN · anaphylaxis
Recent literature (PubMed)
Alopecia areata (AA) is an autoimmune, nonscarring hair loss disorder with slightly greater prevalence in children than adults. Various treatment modalities exist; however, their evidence in pediatric AA patients is lacking. To evaluate the evidence of current treatment modalities for pediatric AA. We conducted a systematic review on the PubMed database in October 2019 for all published articles involving patients <18 years old. Articles discussing AA treatment in pediatric patients were included, as were articles discussing both pediatric and adult patients, if data on individual pediatric patients were available. Inclusion criteria were met by 122 total reports discussing 1032 patients. Reports consisted of 2 randomized controlled trials, 4 prospective comparative cohorts, 83 case series, 2 case-control studies, and 31 case reports. Included articles assessed the use of aloe, apremilast, anthralin, anti-interferon gamma antibodies, botulinum toxin, corticosteroids, contact immunotherapies, cryotherapy, hydroxychloroquine, hypnotherapy, imiquimod, Janus kinase inhibitors, laser and light therapy, methotrexate, minoxidil, phototherapy, psychotherapy, prostaglandin analogs, sulfasalazine, topical calcineurin inhibitors, topical nitrogen mustard, and ustekinumab. English-only articles with full texts were used. Manuscripts with adult and pediatric data were only incorporated if individual-level data for pediatric patients were provided. No meta-analysis was performed. Topical corticosteroids are the preferred first-line treatment for pediatric AA, as they hold the highest level of evidence, followed by contact immunotherapy. More clinical trials and comparative studies are needed to further guide management of pediatric AA and to promote the potential use of pre-existing, low-cost, and novel therapies, including Janus kinase inhibitors.
To update the existing European Alliance of Associations for Rheumatology (EULAR) points to consider (PtC) for use of antirheumatic drugs in reproduction, pregnancy, and lactation, including additional drugs and adverse outcomes as well as paternal drug safety. According to the EULAR standardised operating procedures, an international task force (TF) defined the questions for a systematic literature review, followed by formulation of the updated statements. A predefined voting process was applied to each overarching principle and statement. Level of evidence and strength of recommendation were assigned, and participants finally provided their level of agreement for each item. The TF proposes 5 overarching principles and 12 recommendations for the use of antirheumatic drugs before and during pregnancy, through lactation, and in male patients. The current evidence indicates that synthetic disease-modifying antirheumatic drugs (DMARDs) compatible with pregnancy include antimalarials, azathioprine, colchicine, cyclosporine, sulfasalazine, and tacrolimus. Regarding nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, a more restrictive approach to their use during pregnancy is recommended. Based on an individualised risk-benefit assessment, all tumour necrosis factor inhibitor (TNFi) biologic DMARDs (bDMARDs) can be used throughout pregnancy, and non-TNFi bDMARDs may be used if needed. In relation to lactation, compatible drugs include antimalarials, azathioprine, colchicine, cyclosporine, glucocorticoids, intravenous immunoglobulin (IVIG), NSAIDs, sulfasalazine, and tacrolimus. All bDMARDs are considered compatible with breastfeeding. Concerning the use of drugs in men, compatible options include antimalarials, azathioprine, colchicine, cyclosporine, IVIG, leflunomide, methotrexate, mycophenolate, NSAIDs, glucocorticoids, sildenafil, sulfasalazine, tacrolimus, and bDMARDs. The updated recommendations provide consensus guidance and will help to improve the
Ferroptosis is a type of regulated cell death characterized by intracellular accumulation of iron and reactive oxygen species, inhibition of system Xc-, glutathione depletion, nicotinamide adenine dinucleotide phosphate oxidation and lipid peroxidation. Since its discovery and characterization in 2012, many efforts have been made to reveal the underlying mechanisms, modulating compounds, and its involvement in disease pathways. Ferroptosis inducers include erastin, sorafenib, sulfasalazine and glutamate, which, by inhibiting system Xc-, prevent the import of cysteine into the cells. RSL3, statins, Ml162 and Ml210 induce ferroptosis by inhibiting glutathione peroxidase 4 (GPX4), which is responsible for preventing the formation of lipid peroxides, and FIN56 and withaferin trigger GPX4 degradation. On the other side, ferroptosis inhibitors include ferrostatin-1, liproxstatin-1, α-tocopherol, zileuton, FSP1, CoQ10 and BH4, which interrupt the lipid peroxidation cascade. Additionally, deferoxamine, deferiprone and N-acetylcysteine, by targeting other cellular pathways, have also been classified as ferroptosis inhibitors. Increased evidence has established the involvement of ferroptosis in distinct brain diseases, including Alzheimer's, Parkinson's and Huntington's diseases, amyotrophic lateral sclerosis, multiple sclerosis, and Friedreich's ataxia. Thus, a deep understanding of how ferroptosis contributes to these diseases, and how it can be modulated, can open a new window of opportunities for novel therapeutic strategies and targets. Other studies have shown a sensitivity of cancer cells with mutated RAS to ferroptosis induction and that chemotherapeutic agents and ferroptosis inducers synergize in tumor treatment. Thus, it is tempting to consider that ferroptosis may arise as a target mechanistic pathway for the treatment of brain tumors. Therefore, this work provides an up-to-date review on the molecular and cellular mechanisms of ferroptosis and their involvement i
This study aims to provide an update of the European Alliance of Associations for Rheumatology (EULAR) rheumatoid arthritis (RA) management recommendations addressing the most recent insights. An International Task Force was formed with a wide expertise and solicited 2 systemic literature research activities on the safety and efficacy of disease-modifying antirheumatic drugs (DMARDs). New evidence was discussed, considering the update from 2022. A voting process was applied to each item. Levels of evidence and strengths of recommendation were assigned, and participants voted on the levels of agreement. The task force agreed on 5 overarching principles and reduced the number of recommendations to 9 concerning use of conventional synthetic DMARDs (methotrexate [MTX], leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b)DMARDs (tumour necrosis factor inhibitors [adalimumab, certolizumab pegol, etanercept, golimumab, infliximab], abatacept, rituximab, tocilizumab, sarilumab, including biosimilars) and targeted synthetic [ts]DMARDs (namely the Janus kinase inhibitors [JAKi] tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target), and tapering following clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were considered. Initially, MTX ideally in combination with short-term GCs is recommended; upon insufficient response after 3 to 6 months, a bDMARD should be added; after careful consideration of risks, including MACEs, malignancies and/or thrombo-embolic events, JAKi may also be considered. If the first bDMARD (or JAKi) fails, any other bDMARD (from another or the same class) or JAKi (considering risks) is recommended. With sustained remission, DMARDs may be tapered, but caution is required as stopping often leads to a flare. Levels of evidence and levels of agreement were hig
Crohn's Disease (CD) is a chronic inflammatory disease that can lead to progressive damage to the gastrointestinal tract and significant disability. Early, "top-down" biologic therapy is recommended in moderate-to-severe CD to induce remission and to prevent hospitalization and complications. However, an estimated 20-30% of patients with CD have a mild disease course and may not garner sufficient benefit from expensive, immunosuppressing agents to justify their risks. Herein, we review characteristics of patients with mild CD, the available options for disease treatment and monitoring, and future directions of research. For ambulatory outpatients with low-risk, mild, ileal or ileocolonic CD, induction of remission with budesonide is recommended. For colonic CD, sulfasalazine is a reasonable choice, although other aminosalicylates have no role in the treatment of CD. No large, randomized trial has supported the use of antibiotics or antimycobacterials in the treatment of CD. Partial Enteral Nutrition and Crohn's Disease Exclusion Diets may be appropriate for inducing remission in some adult patients, with trials ongoing. Select patients with mild-to-moderate CD may benefit from maintenance therapy with azathioprines or gut specific biologics, such as vedolizumab. The role of complementary and alternative medicine is not well defined. The identification, risk stratification, and monitoring of patients with mild CD can be a challenging clinical scenario. Some patients with low risk of disease progression may be appropriate for initial induction of remission with budesonide or sulfasalazine, followed by close clinical monitoring. Future research should focus on pre-clinical biomarkers to stratify disease, novel therapies with minimal systemic immune suppression, and validation of rigorous clinical monitoring algorithms.