Teratogenicity study of the dihydroorotate-dehydrogenase inhibitor and protein tyrosine kinase inhibitor Leflunomide in mice

Fukushima, Ryou; Kanamori, Shuichi; Hirashiba, Masahiro; Hishikawa, Atsuko; Muranaka, Ri-ich; Kaneto, Masako; Nakamura, Kazuichi; Kato, Ikuo

doi:10.1016/j.reprotox.2007.05.006

Cited by 73 publications

(52 citation statements)

References 13 publications

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“…Inhibition of cyclooxygenase enzymes -1 and -2 (Gasparini et al, 2003) Modulation of the synthesis of fibronectin (Ernst et al, 1995), various types of collagen (Ernst et al, 1995;Liu et al, 2007), large chondroitin sulfate proteoglycans (Okada et al, 1994), and HA (Sussmann et al, 2004); suppression of MMP expression, synthesis, and activity (Sadowski and Steinmeyer, 2001;Pavlovic et al, 2006) Other immunosuppressive drugs Cyclosporine A Calcineurin inhibitor (Ho et al, 1996) Differential effect on collagen synthesis and fibrosis (Eickelberg et al, 2001;Fornoni et al, 2001;Waller et al, 2004); inhibition of MMP activity (Fornoni et al, 2001;Chiu et al, 2009;Saygili et al, 2009) Leflunomide Pyrimidine synthesis inhibitor (Fukushima et al, 2007) Inhibitory effect on fibrogenesis (Yao et al, 2004;Si et al, 2007) Methotrexate Inhibitor of dihydrofolate reductase (Warren et al, 2008) Reduction of type IV collagen synthesis and ECM expansion (Yozai et al, 2005); influence on MMP and TIMP production …”

Section: A Current Anti-inflammatory and Immunomodulatory Drugs Withmentioning

confidence: 99%

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

et al. 2009

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Section: A Current Anti-inflammatory and Immunomodulatory Drugs Withmentioning

confidence: 99%

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

et al. 2009

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“…Like methotrexate, this medication is profoundly teratogenic in animals [ 58 ]. There are few case reports of congenital anomalies of infants exposed to this medication in utero [ 59 ].…”

Section: Lefl Unomidementioning

confidence: 99%

The Medical Management of the Rheumatology Patient During Pregnancy

Bermas

2014

Contraception and Pregnancy in Patients With Rheumatic Disease

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Congenital anomalies occur in 3 % of normal pregnancies [ 1 ]. Therefore, risk assessment of any particular agent during pregnancy needs to take into account this background rate of teratogenicity. For many years, clinicians relied on the FDA risk categories (A, B, C, D, and X) to assess drugs for safety for use in pregnancy. As Briggs, author of the major textbook in this fi eld, points out, these risk assessments are limited because they are "confusing and simplistic" and incorrectly gave the impression that risk increases from category to category [ 2 ]. The FDA is currently considering new labeling for pregnancy risk. The approach this chapter will take is to present the available data on medication safety in pregnancy and lactation and to synthesize the information regarding drug safety.Each pregnant woman has her own view about assuming risk during her pregnancy. For example, some women will avoid any substance that could have potential risk during pregnancy (caffeine, over-the-counter medications, food-additives) while other women will be willing to assume some risk and modify their ingestion of these substances. Similarly, treating physicians have varying tolerance to risk. While one clinician may be willing to prescribe TNF-α blockers during pregnancy, others will be uncomfortable recommending these medications. Therefore, when approaching management decisions of rheumatic diseases during pregnancy, it is helpful for the treating clinician to be aware of both the patient's and their own risk tolerance, in addition to the available medical data. To this end, up-front discussions prior to conception or early in pregnancy regarding what medications may be used safely and comfortably in the case of a disease fl are are ideal.

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“…The teratogenic potential of leflunomide and teriflunomide has been demonstrated in animals [71,72], although the teratogenic risk of teriflunomide in humans has not been well characterized. The FDA categorizes teriflunomide into pregnancy risk category X.…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

Oral drugs in multiple sclerosis therapy: an overview and a critical appraisal

D’Amico

Leone

Caserta

et al. 2015

Expert Review of Neurotherapeutics

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Multiple sclerosis (MS) is characterized by demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of MS resulted in the introduction of numerous effective drugs with diverse mechanisms of actions, routes of administration and benefit-risk profiles. New oral drugs recently approved for MS treatment has led to significant achievements in MS management. The oral route of administration promotes patient satisfaction and increases therapeutic compliance; but their introduction has raised concerns regarding safety and tolerability; and a thorough analysis of the benefit/risk ratio is required. This article reviews the mechanisms of action, safety and efficacy of the licensed and experimental oral drugs in MS. Moreover, we put into perspective the disease, drug and patient-related factors that should be taken into account when considering the appropriate oral drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.

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Teratogenicity study of the dihydroorotate-dehydrogenase inhibitor and protein tyrosine kinase inhibitor Leflunomide in mice

Cited by 73 publications

References 13 publications

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy

The Medical Management of the Rheumatology Patient During Pregnancy

Oral drugs in multiple sclerosis therapy: an overview and a critical appraisal

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