Pharmacy Policy Bulletin

Title: Ophthalmic Policy #: Rx.01.123

Application of pharmacy policy is determined by benefits and contracts. Benefits may vary based on product line, group, or contract. Some medications may be subject to precertification, age, gender or quantity restrictions. Individual member benefits must be verified.

This pharmacy policy document describes the status of pharmaceutical information and/or technology at the time the document was developed. Since that time, new information relating to drug efficacy, interactions, contraindications, dosage, administration routes, safety, or FDA approval may have changed. This Pharmacy Policy will be regularly updated as scientific and medical literature becomes available. This information may include new FDA-approved indications, withdrawals, or other FDA alerts. This type of information is relevant not only when considering whether this policy should be updated, but also when applying it to current requests for coverage.

Members are advised to use participating pharmacies in order to receive the highest level of benefits. Intent: (Zioptan®) and (Rescula®) are approved for reducing elevated intraocular pressure (IOP) in patients with open-angle or .

The use of tafluprost (Zioptan®) and unoprostone (Rescula®) requires prior authorization (i.e. clinical pharmacist and/or Medical Director review).

Description: Tafluprost (Zioptan®) and unoprostone (Rescula®) belong to a group of drugs classified as selective FP prostanoidreceptor . The pharmacologic activity of tafluprost is hypothesized to be comparable with other analogues.

Tafluprost is a fluorinated analogue of . Corneal esterases rapidly convert tafluprost into its active metabolite, tafluprost acid, and subsequently penetrate into the anterior chamber of the eye. Studies have indicated that tafluprost has potent and selective agonistic activity of the human FP , with minimal activity at other receptors. It has been reported to have 2.8- to 12-times greater affinity to the prostanoid FP receptor compared with . Tafluprost lowers IOP by stimulating the increase of aqueous humor outflow through the uveoscleral passage.

Policy: Tafluprost (Zioptan®) or Unoprostone (Rescula®) is approved when there is documentation of inadequate response or inability to tolerate BOTH of the following: 1. Latanoprost or 2. Lumigan or Travatan Z Black Box Warning: None Guidelines: Refer to the specific manufacturer's prescribing information for administration and dosage details and any applicable Black Box warnings.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, the applicable drug(s) identified in this policy is (are) covered under the pharmacy benefits of the Company’s products when the medical necessity criteria listed in this pharmacy policy are met. Any services that are experimental/investigational or cosmetic are benefit contract exclusions for all products of the Company. References: Aihara M. Clinical appraisal of tafluprost in the reduction of elevated intraocular pressure (IOP) in open-angle glaucoma and ocular hypertension. Clin Ophthalmol. 2010;24(4):163-170.

Chabi A, Varma R, Tsai JC, et al. Randomized clinical trial of the efficacy and safety of preservative- free tafluprost and in patients with open-angle glaucoma or ocular hypertension [published online ahead of print February 4, 2012]. Am J Ophthalmol. DOI: 10.1016/j.ajo.2011.11.008.

Cox EM. New drug application approval letter: Zioptan (NDA 202514). Food and Drug Administration website. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2012/202514s000ltr.pdf. Published February 10, 2012. Accessed June 19, 2014.

Egorov E, Ropo A; Investigators. Adjunctive use of tafluprost with timolol provides additive effects for reduction of intraocular pressure in patients with glaucoma. Eur J Ophthalmol. 2009;19(2):214-222.

Erb C, Lanzl I, Seidova S, Kimmich F. Preservative-free tafluprost 0.0015% in the treatment of patients with glaucoma and ocular hypertension. Adv Ther. 2011;28(7):575-585.

Facts and Comparisons Website [Rescula]. Available at www.factsandcomparisons.com. Accessed June 13, 2014.

Hommer A, Kimmich F. Switching patients from preserved prostaglandin-analog monotherapy to preservative-free tafluprost. Clin Ophthalmol. 2011;5:623-631.

Iwase A, Suzuki Y, Araie M, et al; Tajimi Study Group, Japan Glaucoma Society. The prevalence of primary open-angle glaucoma in Japanese: the Tajimi Study. Ophthalmology. 2004;111(9):1641-1648.

Janulevičienė I, Derkač I, Grybauskiene L, Paulauskaitė R, Gromnickaite R, Kuzmienė L. Effects of preservative-free tafluprost on tear film osmolarity, tolerability, and intraocular pressure in previously treated patients with open-angle glaucoma. Clin Ophthalmol. 2012;6:103-109.

Kurashima H, Watabe H, Sato N, Abe S, Ishida N, Yoshitomi T. Effects of prostaglandin F(2α) analogues on endothelin-1-induced impairment of rabbit ocular blood flow: comparison among tafluprost, travoprost, and latanoprost. Exp Eye Res. 2010;91(6):853-859.

Merck announces FDA acceptance of new drug application for investigational ophthalmic medication SAFLUTAN (tafluprost) [news release]. Whitehouse Station, NJ: Merck; March 9, 2011. http://www.merck.com/newsroom/news-release-archive/research-and-development/home.html. Accessed June 19, 2014.

Mochizuki H, Itakura H, Yokoyama T, Takamatsu M, Kiuchi Y. Twenty-four-hour ocular hypotensive effects of 0.0015% tafluprost and 0.005% latanoprost in healthy subjects. Jpn J Ophthalmol. 2010;54(4):286-290.

Nakano T, Yoshikawa K, Kimura T, Suzumura H, Nanno M, Noro T. Efficacy and safety of tafluprost in normal-tension glaucoma with intraocular pressure of 16 mmHg or less. Jpn J Ophthalmol. 2011;55(6):605-613.

Pantcheva MB, Seibold LK, Awadallah NS, Kahook MY. Tafluprost: a novel prostaglandin analog for treatment of glaucoma. Adv Ther. 2011;28(9):707-715.

Pozarowska D. Safety and tolerability of tafluprost in treatment of elevated intraocular pressure in open-angle glaucoma and ocular hypertension. Clin Ophthalmol. 2010;4:1229-1236.

Prostaglandin . Facts & Comparisons [database online]. St. Louis, MO: Wolters Kluwer Health Inc; 2012. Accessed June 19, 2014.

Schnober D, Hofmann G, Maier H, Scherzer ML, Ogundele AB, Jasek MC. Diurnal IOP-lowering efficacy and safety of travoprost 0.004% compared with tafluprost 0.0015% in patients with primary open-angle glaucoma or ocular hypertension. Clin Ophthalmol. 2010; 4:1459-1463.

Takagi Y, Nakajima T, Shimazaki A, et al. Pharmacological characteristics of AFP-168 (tafluprost), a new prostanoid FP receptor agonist, as an ocular hypotensive drug. Exp Eye Res. 2004;78(4):767- 776.

Traverso CE, Ropo A, Papadia M, Uusitalo H. A phase II study on the duration and stability of the intraocular pressure-lowering effect and tolerability of tafluprost compared with latanoprost. J Ocul Pharmacol Ther. 2010;26(1):97-104.

Uusitalo H, Kaarniranta K, Ropo A. , efficacy and safety profiles of preserved and preservative-free tafluprost in healthy volunteers. Acta Ophthalmol Suppl (Oxf). 2008;242:7-13.

Uusitalo H, Pillunat LE, Ropo A; Phase III Study Investigators. Efficacy and safety of tafluprost 0.0015% versus latanoprost 0.005% eye drops in open-angle glaucoma and ocular hypertension: 24- month results of a randomized, double-masked phase III study. Acta Ophthalmol. 2010;88(1):12-19.

Zioptan [package insert]. Whitehouse Station, NJ: Merck & Co Inc; September 2013. Accessed June 13, 2014. Applicable Drugs: Inclusion of a drug in this table does not imply coverage. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply. Generic Brand Name Name Zioptan Tafluprost Rescula Unoprostone

Cross References:

Policy Version Number: 3.00 P&T Approval Date: July 10, 2014 Policy Effective Date: August 01, 2014 Next Required Review Date: July 10, 2015

The Policy Bulletins on this website were developed to assist AmeriHealth in administering the provisions of the respective benefit programs, and do not constitute a contract. If you are an AmeriHealth member, please refer to your specific benefit program for the terms, conditions, limitations and exclusions of your coverage. AmeriHealth does not provide health care services, medical advice or treatment, or guarantee the outcome or results of any medical services/treatments. The facility and professional providers are responsible for providing medical advice and treatment. Facility and professional providers are independent contractors and are not employees or agents of AmeriHealth. If you have a specific medical condition, please consult with your doctor. AmeriHealth reserves the right at any time to change or update its Policy Bulletins. ©2014 AmeriHealth, Inc. All Rights Reserved.