Body of evidence and approaches applied in the clinical development programme of fixed‐dose combinations in the European Union from 2010 to 2016

Nøhr-Nielsen, Asbjørn; Bruin, Marie L. De; Thomsen, Mikael S.; Pipper, Christian Bressen; Lange, Theis; Bjerrum, Ole J.; Lund, Trine Meldgaard

doi:10.1111/bcp.13986

Cited by 7 publications

(5 citation statements)

References 22 publications

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“…After development, additional regulatory requirements must be considered during the application for the marketing authorization of new FDCs [ 126 ]. According to the European Guideline on the clinical development of fixed-combination medicinal products (EMA/CVMP/83804/2005), the basic scientific requirements for any fixed-combination medicinal product are as follows [ 128 , 129 ]: Justification and rationale for the combination. Demonstration of the contribution of all active substances to the desired therapeutic effect.…”

Section: Parenteral Fixed-dose Combinationsmentioning

confidence: 99%

Parenteral Ready-to-Use Fixed-Dose Combinations Including NSAIDs with Paracetamol or Metamizole for Multimodal Analgesia—Approved Products and Challenges

Silva,

Costa,

Veiga

et al. 2023

Pharmaceuticals

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The combination of non-steroidal anti-inflammatory drugs (NSAIDs) with non-opioid analgesics is common in clinical practice for the treatment of acute painful conditions like post-operative and post-traumatic pain. Despite the satisfactory results achieved by oral analgesics, parenteral analgesia remains a key tool in the treatment of painful conditions when the enteral routes of administration are inconvenient. Parenteral ready-to-use fixed-dose combinations of non-opioid analgesics combinations, including NSAIDs and paracetamol or metamizole, could play a central role in the treatment of painful conditions by combining the advantages of multimodal and parenteral analgesia in a single formulation. Surprisingly, only in 2020, a parenteral ready-to-use fixed-dose combination of ibuprofen/paracetamol was launched to the market. This review aims to investigate the current availability of combinations of NSAIDs with paracetamol or metamizole in both European and American markets, and how the combination of such drugs could play a central role in a multimodal analgesia strategy. Also, we explored how the parenteral formulations of NSAIDs, paracetamol, and metamizole could serve as starting elements for the development of new parenteral ready-to-use fixed-dose combinations. We concluded that, despite the well-recognized utility of combining NSAIDs with paracetamol or metamizole, several randomized clinical trial studies demonstrate no clear advantages concerning their efficacy and safety. Future clinical trials specifically designed to assess the efficacy and safety of pre-formulated fixed-dose combinations are required to generate solid evidence about their clinical advantages.

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Section: Parenteral Fixed-dose Combinationsmentioning

confidence: 99%

Parenteral Ready-to-Use Fixed-Dose Combinations Including NSAIDs with Paracetamol or Metamizole for Multimodal Analgesia—Approved Products and Challenges

Silva,

Costa,

Veiga

et al. 2023

Pharmaceuticals

View full text Add to dashboard Cite

show abstract

“…After development, additional regulatory requirements must be considered during the application for the marketing authorization of new FDCs [126]. According to the European Guideline on the clinical development of fixed-combination medicinal products (EMA/CVMP/83804/2005), the basic scientific requirements for any fixed-combination medicinal product are as follows [128,129]:…”

Section: Other Nsaid-based Combinationsmentioning

confidence: 99%

Parenteral Ready-to-Use Fixed-Dose Combinations of NSAIDs for Multimodal Analgesia – An overview of approved products and challenges

Silva¹,

Costa²,

Veiga³

et al. 2023

Preprint

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The combination of non-steroidal anti-inflammatory drugs (NSAIDs) with non-opioid analgesics is common in clinical practice for the treatment of acute pain conditions like post-operative and post-traumatic pain. Besides that, and despite the very satisfactory results achieved by oral analgesics, parenteral analgesia is a key tool in the treatment of painful conditions when the enteral routes are not convenient. The parenteral ready-to-use fixed-dose combinations of NSAIDs with non-opioid analgesics like paracetamol or metamizole could play a central role in the treatment of painful conditions since they are able to gather into only one formulation the advantages of multimodal and parenteral analgesia. Surprisingly, only very recently a parenteral ready-to-use fixed-dose combination of Ibuprofen/Paracetamol was launched to the market. This review aims to review the current availability of NSAID-based Parenteral Fixed-dose combinations with paracetamol and metamizole in the European and American markets, and how the combination of such drugs could play a central role in a multimodal analgesia strategy. Also, it is explored how the parenteral formulations of NSAIDs, paracetamol, and metamizole could serve as starting elements for the development of new parenteral ready-to-use fixed-dose combinations. With this review, we concluded that, despite the well-recognized utility of combining NSAIDs with non-opioid analgesics, there are in the literature several randomized clinical trial studies unable to demonstrate clear advantages concerning their efficacy and safety. In the future, it is deemed necessary to perform clinical trials specifically designed to assess the efficacy and safety of these fixed-dose formulations to generate solid evidence of their clinical advantages.

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“…In the US, STCT approvals rose from 12 approvals in the 1980s to 59 approvals in the 2000s, 18 while in Europe, 7 STCTs were approved in 2016, compared with just 1 in 2010. 19 STCTs are now available for hypertension, HIV, asthma, diabetes, and other chronic diseases. The evaluation of STCT use is relevant to multiple stakeholders, including patients, clinicians, caregivers, and payers.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of Single-Tablet Combination Therapy in Improving Adherence and Persistence and the Relation to Clinical and Economic Outcomes

Paoli,

Linder,

Gurjar

et al. 2024

Journal of Health Economics and Outcomes Research

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Background: Single-tablet combination therapies (STCTs) combine multiple drugs into one formulation, making drug administration more convenient for patients. STCTs were developed to address concerns with treatment adherence and persistence, but the impact of STCT use is not fully understood across indications. Objectives: We conducted a systematic literature review (SLR) to examine STCT-associated outcomes across 4 evidence domains: clinical trials, real-world evidence (RWE), health-related quality of life (HRQoL) studies, and economic evaluations. Methods: Four SLRs were conducted across the aforementioned domains. Included studies compared STCTs as well as fixed-dose combinations ([FDCs] of non-tablet formulations) with the equivalent active compounds and doses in loose-dose combinations (LDCs). Original research articles were included; case reports, case series, and non-English-language sources were excluded. Databases searched included EconLit, Embase, and Ovid MEDLINE® ALL. Two independent reviewers assessed relevant studies and extracted data. Conflicts were resolved with a third reviewer or consensus-based discussion. Results: In all, 109 studies were identified; 27 studies were identified in more than one SLR. Treatment adherence was significantly higher in patients receiving FDCs vs LDCs in 12 of 13 RWE studies and 3 of 13 clinical trials. All 18 RWE studies reported higher persistence with FDCs. In RWE studies examining clinical outcomes (n = 17), 14 reported positive findings with FDCs, including a reduced need for add-on medication, blood pressure control, and improved hemoglobin A1C. HRQoL studies generally reported numerical improvements with STCTs or similarities between STCTs and LDCs. Economic outcomes favored STCT use. All 6 cost-effectiveness or cost-utility analyses found FDCs were less expensive and more efficacious than LDCs. Four budget impact models found that STCTs were associated with cost savings. Medical costs and healthcare resource use were generally lower with FDCs than with LDCs. Discussion: Evidence from RWE and economic studies strongly favored STCT use, while clinical trials and HRQoL studies primarily reported similarity between STCTs and LDCs. This may be due to clinical trial procedures aimed at maximizing adherence and HRQoL measures that are not designed to evaluate drug administration. Conclusions: Our findings highlight the value of STCTs for improving patient adherence, persistence, and clinical outcomes while also offering economic advantages.

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Body of evidence and approaches applied in the clinical development programme of fixed‐dose combinations in the European Union from 2010 to 2016

Cited by 7 publications

References 22 publications

Parenteral Ready-to-Use Fixed-Dose Combinations Including NSAIDs with Paracetamol or Metamizole for Multimodal Analgesia—Approved Products and Challenges

Parenteral Ready-to-Use Fixed-Dose Combinations Including NSAIDs with Paracetamol or Metamizole for Multimodal Analgesia—Approved Products and Challenges

Parenteral Ready-to-Use Fixed-Dose Combinations of NSAIDs for Multimodal Analgesia – An overview of approved products and challenges

Effectiveness of Single-Tablet Combination Therapy in Improving Adherence and Persistence and the Relation to Clinical and Economic Outcomes

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