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Erschienen in: Drugs 8/2015

01.05.2015 | Adis Drug Evaluation

Diquafosol Ophthalmic Solution 3 %: A Review of Its Use in Dry Eye

verfasst von: Gillian M. Keating

Erschienen in: Drugs | Ausgabe 8/2015

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Abstract

Diquafosol ophthalmic solution 3 % (Diquas®) is a P2Y2 receptor agonist that promotes tear fluid and mucin secretion and is currently approved in Japan and South Korea for the treatment of dry eye. In randomized, double-blind, multicentre trials in patients with dry eye, significantly greater improvements in fluorescein and rose bengal staining scores were seen with diquafosol ophthalmic solution 3 % than with placebo, and diquafosol ophthalmic solution 3 % was noninferior to sodium hyaluronate ophthalmic solution 0.1 % in terms of the improvement in the fluorescein staining score and more effective than sodium hyaluronate ophthalmic solution 0.1 % in terms of the improvement in the rose bengal staining score. The efficacy of diquafosol ophthalmic solution 3 % in the treatment of dry eye was maintained in the longer term, with improvements also seen in subjective dry eye symptoms, and was also shown in a real-world setting. Diquafosol ophthalmic solution 3 % also demonstrated efficacy in various specific dry eye disorders, including aqueous-deficient dry eye, short tear film break-up time dry eye, obstructive meibomian gland dysfunction, dry eye following laser in situ keratomileusis surgery and dry eye following cataract surgery, as well as in contact lens wearers and visual display terminal users. Diquafosol ophthalmic solution 3 % was generally well tolerated in patients with dry eye, with eye irritation the most commonly reported adverse event. In conclusion, diquafosol ophthalmic solution 3 % is a useful option for the treatment of dry eye.
Literatur
1.
Zurück zum Zitat The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye workshop (2007). Ocul Surf. 2007;5(2):93–107 The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye workshop (2007). Ocul Surf. 2007;5(2):93–107
2.
Zurück zum Zitat Foulks GN. Pharmacological management of dry eye in the elderly patient. Drugs Aging. 2008;25(2):105–18.CrossRefPubMed Foulks GN. Pharmacological management of dry eye in the elderly patient. Drugs Aging. 2008;25(2):105–18.CrossRefPubMed
3.
Zurück zum Zitat The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye workshop (2007). Ocul Surf. 2007;5(2):75–92 The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye workshop (2007). Ocul Surf. 2007;5(2):75–92
4.
Zurück zum Zitat Skalicky SE, Petsoglou C, Gurbaxani A, et al. New agents for treating dry eye syndrome. Curr Allergy Asthma Rep. 2013;13(3):322–8.CrossRefPubMed Skalicky SE, Petsoglou C, Gurbaxani A, et al. New agents for treating dry eye syndrome. Curr Allergy Asthma Rep. 2013;13(3):322–8.CrossRefPubMed
5.
Zurück zum Zitat Lau OCF, Samarawickrama C, Skalicky SE. P2Y2 receptor agonists for the treatment of dry eye disease: a review. Clin Ophthalmol. 2014;8:327–34.PubMedCentralPubMed Lau OCF, Samarawickrama C, Skalicky SE. P2Y2 receptor agonists for the treatment of dry eye disease: a review. Clin Ophthalmol. 2014;8:327–34.PubMedCentralPubMed
6.
Zurück zum Zitat Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye workshop (2007). Ocul Surf. 2007;5(2):163–78 Management and therapy of dry eye disease: report of the Management and Therapy Subcommittee of the International Dry Eye workshop (2007). Ocul Surf. 2007;5(2):163–78
7.
Zurück zum Zitat Santen. Diquas® (diquafosol soium) ophthalmic solution 3 %: Japanese prescribing information. 2014 Santen. Diquas® (diquafosol soium) ophthalmic solution 3 %: Japanese prescribing information. 2014
8.
Zurück zum Zitat Pendergast W, Yerxa BR, Douglass JG 3rd, et al. Synthesis and P2Y receptor activity of a series of uridine dinucleoside 5′-polyphosphates. Bioorg Med Chem Lett. 2001;11(2):157–60.CrossRefPubMed Pendergast W, Yerxa BR, Douglass JG 3rd, et al. Synthesis and P2Y receptor activity of a series of uridine dinucleoside 5′-polyphosphates. Bioorg Med Chem Lett. 2001;11(2):157–60.CrossRefPubMed
9.
Zurück zum Zitat Fujihara T, Murakami T, Nagano T, et al. INS365 suppresses loss of corneal epithelial integrity by secretion of mucin-like glycoprotein in a rabbit short-term dry eye model. J Ocul Pharmacol Ther. 2002;18(4):363–70.CrossRefPubMed Fujihara T, Murakami T, Nagano T, et al. INS365 suppresses loss of corneal epithelial integrity by secretion of mucin-like glycoprotein in a rabbit short-term dry eye model. J Ocul Pharmacol Ther. 2002;18(4):363–70.CrossRefPubMed
10.
Zurück zum Zitat Li Y, Kuang K, Yerxa B, et al. Rabbit conjunctival epithelium transports fluid, and P2Y22 receptor agonists stimulate Cl− and fluid secretion. Am J Physiol Cell Physiol. 2001;281:C595–602.PubMed Li Y, Kuang K, Yerxa B, et al. Rabbit conjunctival epithelium transports fluid, and P2Y22 receptor agonists stimulate Cl and fluid secretion. Am J Physiol Cell Physiol. 2001;281:C595–602.PubMed
11.
Zurück zum Zitat Murakami T, Fujihara T, Horibe Y, et al. Diquafosol elicits increases in net Cl− transport through P2Y2 receptor stimulation in rabbit conjunctiva. Ophthalmic Res. 2004;36(2):89–93.CrossRefPubMed Murakami T, Fujihara T, Horibe Y, et al. Diquafosol elicits increases in net Cl transport through P2Y2 receptor stimulation in rabbit conjunctiva. Ophthalmic Res. 2004;36(2):89–93.CrossRefPubMed
12.
Zurück zum Zitat Cowlen MS, Zhang VZ, Warnock L, et al. Localization of ocular P2Y2 receptor gene expression by in situ hybridization. Exp Eye Res. 2003;77(1):77–84.CrossRefPubMed Cowlen MS, Zhang VZ, Warnock L, et al. Localization of ocular P2Y2 receptor gene expression by in situ hybridization. Exp Eye Res. 2003;77(1):77–84.CrossRefPubMed
13.
Zurück zum Zitat Jumblatt JE, Jumblatt MM. Regulation of ocular mucin secretion by P2Y2 nucleotide receptors in rabbit and human conjunctiva. Exp Eye Res. 1998;67(3):341–6.CrossRefPubMed Jumblatt JE, Jumblatt MM. Regulation of ocular mucin secretion by P2Y2 nucleotide receptors in rabbit and human conjunctiva. Exp Eye Res. 1998;67(3):341–6.CrossRefPubMed
14.
Zurück zum Zitat Fujihara T, Murakami T, Fujita H, et al. Improvement of corneal barrier function by the P2Y2 agonist INS365 in a rat dry eye model. Invest Ophthalmol Vis Sci. 2001;42(1):96–100.PubMed Fujihara T, Murakami T, Fujita H, et al. Improvement of corneal barrier function by the P2Y2 agonist INS365 in a rat dry eye model. Invest Ophthalmol Vis Sci. 2001;42(1):96–100.PubMed
15.
Zurück zum Zitat Takaoka-Shichijo Y, Shinomiya K, Katsuta O, et al. Stimulatory action of diquafosol tetrasodium on mucin-like glucoprotein secretion in rabbit conjunctival tissues [in Japanese]. Atarashii Ganka. 2011;28(4):543–8. Takaoka-Shichijo Y, Shinomiya K, Katsuta O, et al. Stimulatory action of diquafosol tetrasodium on mucin-like glucoprotein secretion in rabbit conjunctival tissues [in Japanese]. Atarashii Ganka. 2011;28(4):543–8.
16.
Zurück zum Zitat Takaoka-Shichijo Y, Murakami T, Nakamura M. Stimulatory effect of diquafosol tetrasodium on tear fluid secretion in normal rabbits [in Japanese]. Atarashii Ganka. 2011;28(7):1029–33. Takaoka-Shichijo Y, Murakami T, Nakamura M. Stimulatory effect of diquafosol tetrasodium on tear fluid secretion in normal rabbits [in Japanese]. Atarashii Ganka. 2011;28(7):1029–33.
17.
Zurück zum Zitat Nakamura M, Imanaka T, Sakamoto A. Diquafosol ophthalmic solution for dry eye treatment. Adv Ther. 2012;29(7):579–89.CrossRefPubMed Nakamura M, Imanaka T, Sakamoto A. Diquafosol ophthalmic solution for dry eye treatment. Adv Ther. 2012;29(7):579–89.CrossRefPubMed
18.
Zurück zum Zitat Kojima T, Dogru M, Ibrahim OM, et al. The effects of 3 % diquafosol sodium application on the tear functions and ocular surface of the Cu, Zn-superoxide dismutase-1 (Sod1)-knockout mice. Mol Vis. 2014;20:929–38.PubMedCentralPubMed Kojima T, Dogru M, Ibrahim OM, et al. The effects of 3 % diquafosol sodium application on the tear functions and ocular surface of the Cu, Zn-superoxide dismutase-1 (Sod1)-knockout mice. Mol Vis. 2014;20:929–38.PubMedCentralPubMed
19.
Zurück zum Zitat Hori Y, Maeno T. Effects of diquafosol ophthalmic solutions and rebamipide ophthalmic suspension on tear fluid volume in normal rabbits [in Japanese]. Atarashii Ganka. 2013;30(7):1007–10. Hori Y, Maeno T. Effects of diquafosol ophthalmic solutions and rebamipide ophthalmic suspension on tear fluid volume in normal rabbits [in Japanese]. Atarashii Ganka. 2013;30(7):1007–10.
20.
Zurück zum Zitat Sakamoto A, Takaoka-Shichijo Y, Yamashita N, et al. Combined effect of diquafosol tetrasodium and purified sodium hyaluronate ophthalmic solutions on tear fluid volume in normal rabbits [in Japanese]. Atarashii Ganka. 2012;29(8):1141–5. Sakamoto A, Takaoka-Shichijo Y, Yamashita N, et al. Combined effect of diquafosol tetrasodium and purified sodium hyaluronate ophthalmic solutions on tear fluid volume in normal rabbits [in Japanese]. Atarashii Ganka. 2012;29(8):1141–5.
21.
Zurück zum Zitat Takaoka-Shichijo Y, Sakamoto A, Nakamura M. Effect of diquafosol tetrasodium on MUC5AC secretion by rabbit conjunctival tissues [in Japanese]. Atarashii Ganka. 2011;28(2):261–5. Takaoka-Shichijo Y, Sakamoto A, Nakamura M. Effect of diquafosol tetrasodium on MUC5AC secretion by rabbit conjunctival tissues [in Japanese]. Atarashii Ganka. 2011;28(2):261–5.
22.
Zurück zum Zitat Takaoka-Shichijo Y, Nakamura M. Stimulatory effect of diquafosol tetrasodium on the expression of membrane-binging mucin genes in cultured human corneal epithelial cells [in Japanese]. Atarashii Ganka. 2011;28(3):425–9. Takaoka-Shichijo Y, Nakamura M. Stimulatory effect of diquafosol tetrasodium on the expression of membrane-binging mucin genes in cultured human corneal epithelial cells [in Japanese]. Atarashii Ganka. 2011;28(3):425–9.
23.
Zurück zum Zitat Dota A, Nakamura M. Combined effect of diquafosol tetrasodium and sodium hyaluronate ophthalmic solutions in rat dry eye model [in Japanese]. Atarashii Ganka. 2011;28(10):1477–81. Dota A, Nakamura M. Combined effect of diquafosol tetrasodium and sodium hyaluronate ophthalmic solutions in rat dry eye model [in Japanese]. Atarashii Ganka. 2011;28(10):1477–81.
24.
Zurück zum Zitat Hori Y, Shiba T, Maeno T. Comparison of efficacy between diquafosol ophthalmic solutions and rebamipide ophthalmic suspensions in treatment of rat dry eye model [in Japanese]. Atarashii Ganka. 2014;31(1):105–9. Hori Y, Shiba T, Maeno T. Comparison of efficacy between diquafosol ophthalmic solutions and rebamipide ophthalmic suspensions in treatment of rat dry eye model [in Japanese]. Atarashii Ganka. 2014;31(1):105–9.
25.
Zurück zum Zitat Yokoi N, Kato H, Kinoshita S. Facilitation of tear fluid secretion by 3 % diquafosol ophthalmic solution in normal human eyes. Am J Ophthalmol. 2014;157(1):85–92.CrossRefPubMed Yokoi N, Kato H, Kinoshita S. Facilitation of tear fluid secretion by 3 % diquafosol ophthalmic solution in normal human eyes. Am J Ophthalmol. 2014;157(1):85–92.CrossRefPubMed
26.
Zurück zum Zitat Koh S, Maeda N, Ikeda C, et al. Effect of instillation of eyedrops for dry eye on optical quality. Invest Ophthalmol Vis Sci. 2013;54(7):4927–33.CrossRefPubMed Koh S, Maeda N, Ikeda C, et al. Effect of instillation of eyedrops for dry eye on optical quality. Invest Ophthalmol Vis Sci. 2013;54(7):4927–33.CrossRefPubMed
28.
Zurück zum Zitat Matsumoto Y, Ohashi Y, Watanabe H, et al. Efficacy and safety of diquafosol ophthalmic solution in patients with dry eye syndrome: a Japanese phase 2 clinical trial. Ophthalmology. 2012;119(10):1954–60.CrossRefPubMed Matsumoto Y, Ohashi Y, Watanabe H, et al. Efficacy and safety of diquafosol ophthalmic solution in patients with dry eye syndrome: a Japanese phase 2 clinical trial. Ophthalmology. 2012;119(10):1954–60.CrossRefPubMed
29.
Zurück zum Zitat Takamura E, Tsubota K, Watanabe H, et al. A randomised, double-masked comparison study of diquafosol versus sodium hyaluronate ophthalmic solutions in dry eye patients. Br J Ophthalmol. 2012;96(10):1310–5.CrossRefPubMedCentralPubMed Takamura E, Tsubota K, Watanabe H, et al. A randomised, double-masked comparison study of diquafosol versus sodium hyaluronate ophthalmic solutions in dry eye patients. Br J Ophthalmol. 2012;96(10):1310–5.CrossRefPubMedCentralPubMed
30.
Zurück zum Zitat Yamaguchi M, Tsubota K, Watanabe H, et al. The safety and efficacy of long-term treatment with 3 % diquafosol ophthalmic solution for dry eye [in Japanese]. Atarashii Ganka. 2012;29(4):527–35. Yamaguchi M, Tsubota K, Watanabe H, et al. The safety and efficacy of long-term treatment with 3 % diquafosol ophthalmic solution for dry eye [in Japanese]. Atarashii Ganka. 2012;29(4):527–35.
31.
Zurück zum Zitat Koh S, Ikeda C, Takai Y, et al. Long-term results of treatment with diquafosol ophthalmic solution for aqueous-deficient dry eye. Jpn J Ophthalmol. 2013;57(5):440–6.CrossRefPubMed Koh S, Ikeda C, Takai Y, et al. Long-term results of treatment with diquafosol ophthalmic solution for aqueous-deficient dry eye. Jpn J Ophthalmol. 2013;57(5):440–6.CrossRefPubMed
32.
Zurück zum Zitat Yamaguchi M, Nishijima T, Shimazaki J, et al. Clinical usefulness of diquafosol for real-world dry eye patients: a prospective, open-label, non-interventional, observational study. Adv Ther. 2014;31(11):1169–81.CrossRefPubMed Yamaguchi M, Nishijima T, Shimazaki J, et al. Clinical usefulness of diquafosol for real-world dry eye patients: a prospective, open-label, non-interventional, observational study. Adv Ther. 2014;31(11):1169–81.CrossRefPubMed
33.
Zurück zum Zitat Kamiya K, Nakanishi M, Ishii R, et al. Clinical evaluation of the additive effect of diquafosol tetrasodium on sodium hyaluronate monotherapy in patients with dry eye syndrome: a prospective, randomized, multicenter study. Eye. 2012;26(10):1363–8.CrossRefPubMedCentralPubMed Kamiya K, Nakanishi M, Ishii R, et al. Clinical evaluation of the additive effect of diquafosol tetrasodium on sodium hyaluronate monotherapy in patients with dry eye syndrome: a prospective, randomized, multicenter study. Eye. 2012;26(10):1363–8.CrossRefPubMedCentralPubMed
34.
Zurück zum Zitat Hwang HS, Sung Y-M, Lee WS, et al. Additive effect of preservative-free sodium hyaluronate 0.1 % in treatment of dry eye syndrome with diquafosol 3 % eye drops. Cornea. 2014;33(9):935–41.CrossRefPubMed Hwang HS, Sung Y-M, Lee WS, et al. Additive effect of preservative-free sodium hyaluronate 0.1 % in treatment of dry eye syndrome with diquafosol 3 % eye drops. Cornea. 2014;33(9):935–41.CrossRefPubMed
35.
Zurück zum Zitat Koh S, Maeda N, Ikeda C, et al. Effect of diquafosol ophthalmic solution on the optical quality of the eyes in patients with aqueous-deficient dry eye. Acta Ophthalmol (Copenh). 2014;92(8):e671–5.CrossRef Koh S, Maeda N, Ikeda C, et al. Effect of diquafosol ophthalmic solution on the optical quality of the eyes in patients with aqueous-deficient dry eye. Acta Ophthalmol (Copenh). 2014;92(8):e671–5.CrossRef
36.
Zurück zum Zitat Shimazaki-Den S, Iseda H, Dogru M, et al. Effects of diquafosol sodium eye drops on tear film stability in short BUT type of dry eye. Cornea. 2013;32(8):1120–5.CrossRefPubMed Shimazaki-Den S, Iseda H, Dogru M, et al. Effects of diquafosol sodium eye drops on tear film stability in short BUT type of dry eye. Cornea. 2013;32(8):1120–5.CrossRefPubMed
37.
Zurück zum Zitat Kaido M, Uchino M, Kojima T, et al. Effects of diquafosol tetrasodium administration on visual function in short break-up time dry eye. J Ocul Pharmacol Ther. 2013;29(6):595–603.CrossRefPubMed Kaido M, Uchino M, Kojima T, et al. Effects of diquafosol tetrasodium administration on visual function in short break-up time dry eye. J Ocul Pharmacol Ther. 2013;29(6):595–603.CrossRefPubMed
38.
Zurück zum Zitat Jung HH, Kang YS, Sung MS, et al. Clinical efficacy of topical 3 % diquafosol tetrasodium in short tear film break-up time dry eye [in Korean]. J Korean Ophthalmol Soc. 2015;56(3):339–44.CrossRef Jung HH, Kang YS, Sung MS, et al. Clinical efficacy of topical 3 % diquafosol tetrasodium in short tear film break-up time dry eye [in Korean]. J Korean Ophthalmol Soc. 2015;56(3):339–44.CrossRef
40.
Zurück zum Zitat Arita R, Suehiro J, Haraguchi T, et al. Topical diquafosol for patients with obstructive meibomian gland dysfunction. Br J Ophthalmol. 2013;97(6):725–9.CrossRefPubMedCentralPubMed Arita R, Suehiro J, Haraguchi T, et al. Topical diquafosol for patients with obstructive meibomian gland dysfunction. Br J Ophthalmol. 2013;97(6):725–9.CrossRefPubMedCentralPubMed
41.
Zurück zum Zitat Toda I, Ide T, Fukumoto T, et al. Combination therapy with diquafosol tetrasodium and sodium hyaluronate in patients with dry eye after laser in situ keratomileusis. Am J Ophthalmol. 2014;157(3):616–22.CrossRefPubMed Toda I, Ide T, Fukumoto T, et al. Combination therapy with diquafosol tetrasodium and sodium hyaluronate in patients with dry eye after laser in situ keratomileusis. Am J Ophthalmol. 2014;157(3):616–22.CrossRefPubMed
42.
Zurück zum Zitat Masuda A, Mori Y, Nejima R. Efficacy of long-term treatment with diquafosol sodium for dry eye due to laser in situ keratomileusis [in Japanese]. Atarashii Ganka. 2013;30(2):249–53. Masuda A, Mori Y, Nejima R. Efficacy of long-term treatment with diquafosol sodium for dry eye due to laser in situ keratomileusis [in Japanese]. Atarashii Ganka. 2013;30(2):249–53.
43.
Zurück zum Zitat Mori Y, Nejima R, Masuda A, et al. Effect of diquafosol tetrasodium eye drop for persistent dry eye after laser in situ keratomileusis. Cornea. 2014;33(7):659–62.CrossRefPubMed Mori Y, Nejima R, Masuda A, et al. Effect of diquafosol tetrasodium eye drop for persistent dry eye after laser in situ keratomileusis. Cornea. 2014;33(7):659–62.CrossRefPubMed
44.
Zurück zum Zitat Takeshita T. Effect of diquafosol sodium ophthalmic solution for dry eye after cataract surgery [in Japanese]. Rinsho Ganka. 2013;67(3):327–30. Takeshita T. Effect of diquafosol sodium ophthalmic solution for dry eye after cataract surgery [in Japanese]. Rinsho Ganka. 2013;67(3):327–30.
45.
Zurück zum Zitat Watanabe K. Efficacy and safety of combined 3 % diquafosol sodium and 0.3 % purified sodium hyaluronate for treatment of dry eye in wearers of frequent-replacement of one-day disposable soft contact lenses [in Japanese]. Nihon Contact Lens Gakkaishi. 2014;56:121–5. Watanabe K. Efficacy and safety of combined 3 % diquafosol sodium and 0.3 % purified sodium hyaluronate for treatment of dry eye in wearers of frequent-replacement of one-day disposable soft contact lenses [in Japanese]. Nihon Contact Lens Gakkaishi. 2014;56:121–5.
46.
Zurück zum Zitat Uchino Y, Tsubota K. Effect of switching treatment from existing therapy to 3 % diquafosol sodium eyedrops for dry eye in VDT users [in Japanese]. Atarashii Gankka. 2013;30(6):871–4. Uchino Y, Tsubota K. Effect of switching treatment from existing therapy to 3 % diquafosol sodium eyedrops for dry eye in VDT users [in Japanese]. Atarashii Gankka. 2013;30(6):871–4.
47.
Zurück zum Zitat Gong L, Sun X, Ma Z, et al. A randomised, parallel-group comparison study of diquafosol ophthalmic solution in patients with dry eye in China and Singapore. Br J Ophthalmol. 2015; doi:10.1136/bjophthalmol-2014-306084. Gong L, Sun X, Ma Z, et al. A randomised, parallel-group comparison study of diquafosol ophthalmic solution in patients with dry eye in China and Singapore. Br J Ophthalmol. 2015; doi:10.​1136/​bjophthalmol-2014-306084.
48.
Zurück zum Zitat Takashima Y, Goya K, Matsuo M. Effect of switching from hyaluronate to diquafosol ophthalmic solution for mild dry eye [in Japanese]. Rinsho Ganka. 2013;67(6):929–33. Takashima Y, Goya K, Matsuo M. Effect of switching from hyaluronate to diquafosol ophthalmic solution for mild dry eye [in Japanese]. Rinsho Ganka. 2013;67(6):929–33.
49.
Zurück zum Zitat Tauber J, Davitt WF, Bokosky JE, et al. Double-masked, placebo-controlled safety and efficacy trial of diquafosol tetrasodium (INS365) ophthalmic solution for the treatment of dry eye. Cornea. 2004;23(8):784–92.CrossRefPubMed Tauber J, Davitt WF, Bokosky JE, et al. Double-masked, placebo-controlled safety and efficacy trial of diquafosol tetrasodium (INS365) ophthalmic solution for the treatment of dry eye. Cornea. 2004;23(8):784–92.CrossRefPubMed
Metadaten
Titel
Diquafosol Ophthalmic Solution 3 %: A Review of Its Use in Dry Eye
verfasst von
Gillian M. Keating
Publikationsdatum
01.05.2015
Verlag
Springer International Publishing
Erschienen in
Drugs / Ausgabe 8/2015
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI
https://doi.org/10.1007/s40265-015-0409-7

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