Alendronate-Induced Esophagitis: Possible Pathogenic Role of Hypersensitivity to Alendronate

Naniwa, Taio; Maeda, Tomoyo; Mizoshita, Tsutomu; Hayami, Yoshihito; Watanabe, Maiko; Banno, Shogo; Ito, Rei

doi:10.2169/internalmedicine.47.1457

Cited by 26 publications

(19 citation statements)

References 11 publications

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“…In the case presented by Brinkmeier et al [37], skin lesions developed after months of alendronate intake and showed a prolonged healing time after cessation of the drug, suggesting a cellular immune response to alendronate. Naniwa et al [22] described an esophageal event related to alendronate with no CPT, but with a positive lymphocyte stimulation test suggesting a delayed hypersensitivity reaction.…”

Section: Discussionmentioning

confidence: 99%

“…BPs have a relatively good safety profile, but the following severe adverse events have been reported: gastrointestinal discomfort, esophageal malignancy, acute-phase reaction, renal failure, hypocalcemia and secondary hyperparathyroidism, musculoskeletal pain, ocular side effect, osteonecrosis of the jaw, atrial fibrillation, atypical fractures of the subtrochanteric and diaphyseal femur, hepatitis and cutaneous adverse drug reactions (CADRs) (table 2, 3) [2,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35]. …”

Section: Introductionmentioning

confidence: 99%

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Bisphosphonate-Induced Cutaneous Adverse Events: The Difficulty of Assessing Imputability through Patch Testing

Barrantes-González¹,

Espona-Quer²,

Salas³

et al. 2014

Dermatology

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Background: Cutaneous adverse drug reactions (CADRs) due to bisphosphonates (BPs) have been scarcely described in the literature. Objective: To discuss the diagnostic value and limitations of cutaneous provocation tests with BPs. Methods: A descriptive case series study with a control group of CADRs due to BPs studied using patch testing from 2005 to 2010 is presented. Results: Patient 1 showed a positive D4++ with alendronate at 1% in petrolatum and D4+++ with alendronate at 1 and 0.1% in water. Patient 2 showed a positive intradermal test D3++ with alendronate at 0.1% in water. Patient 3 showed a positive patch test D4+ with ibandronate at 1% in petrolatum and D4++ with ibandronate at 1% in water, and a positive intradermal test D3+++ with ibandronate at 0.1% in water. Conclusion: Establishing a correct interpretation of a patch test reaction is difficult based just on cutaneous test results. Too high concentrations of the drug can cause irritation and too low concentrations can be responsible of false-negative test reactions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bisphosphonate-Induced Cutaneous Adverse Events: The Difficulty of Assessing Imputability through Patch Testing

Barrantes-González¹,

Espona-Quer²,

Salas³

et al. 2014

Dermatology

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“…However, the oral bioavailability (BA) of alendronate is quite low (1%–2%) due to its high polarity and hydrophilicity (partition coefficient < 1 × 10 −4 ), and food can strongly suppress the intestinal absorption of alendronate 5. In addition, oral administration of alendronate is associated with mucosal damage and disorders, including gastritis, gastric ulcer, and erosive esophagitis 6–8. Therefore, it is highly desirable to develop new delivery systems that improve both the BA and safety of alendronate.…”

Section: Introductionmentioning

confidence: 99%

Development of Polyethylene Glycol-Conjugated Alendronate, a Novel Nitrogen-Containing Bisphosphonate Derivative: Evaluation of Absorption, Safety, and Effects After Intrapulmonary Administration in Rats

Katsumi

Takashima

Sano

et al. 2011

Journal of Pharmaceutical Sciences

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“…However, the oral bioavailability (BA) of alendronate is approximately 0.9% to 1.8% 14. In addition, the oral administration of alendronate has been associated with mucosal damage, including gastritis, gastric ulcer, and erosive esophagitis 15–17. To prevent these adverse effects of alendronate, patients with osteoporosis should sit up or walk for more than 30 minutes after oral administration 18, 19.…”

Section: Introductionmentioning

confidence: 99%

Development of a novel transdermal patch of alendronate, a nitrogen-containing bisphosphonate, for the treatment of osteoporosis

Kusamori

Katsumi

Abe

et al. 2010

Journal of Bone and Mineral Research

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Bisphosphonates are widely used for the treatment and prevention of bone diseases, including Paget disease, hypercalcemia of malignancy, and postmenopausal osteoporosis. In this study, we developed a novel transdermal patch of alendronate, a nitrogencontaining bisphosphonate, for the treatment of bone diseases. The maximum permeation fluxes of alendronate through rat and human skin after application of this patch were 1.9 and 0.3 mg/cm 2 per hour, respectively. The bioavailability (BA) of alendronate in rats was approximately 8.3% after the application of alendronate patch and approximately 1.7% after oral administration. These results indicated that the transdermal permeation of alendronate using this patch system was sufficient for the treatment of bone diseases. The plasma calcium level was effectively reduced after application of the alendronate patch in 1a-hydroxyvitamin D 3 -induced hypercalcemia model rats. The alendronate patch also effectively suppressed the decrease in bone mass in model rats with osteoporosis. Modest alendronateinduced erythema of rat skin was observed after application of the alendronate patch. Incorporation of butylhydroxytoluene in the alendronate patch almost completely suppressed this alendronate-induced skin damage while maintaining the transdermal permeation and pharmacologic effects of alendronate. These findings indicate that our novel transdermal delivery system for alendronate is a promising approach to improve compliance and quality of life of patients in the treatment of bone diseases. ß

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Alendronate-Induced Esophagitis: Possible Pathogenic Role of Hypersensitivity to Alendronate

Abstract: Abstract

Cited by 26 publications

References 11 publications

Bisphosphonate-Induced Cutaneous Adverse Events: The Difficulty of Assessing Imputability through Patch Testing

Bisphosphonate-Induced Cutaneous Adverse Events: The Difficulty of Assessing Imputability through Patch Testing

Development of Polyethylene Glycol-Conjugated Alendronate, a Novel Nitrogen-Containing Bisphosphonate Derivative: Evaluation of Absorption, Safety, and Effects After Intrapulmonary Administration in Rats

Development of a novel transdermal patch of alendronate, a nitrogen-containing bisphosphonate, for the treatment of osteoporosis

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