CENTENE
Corporation

Clinical Policy: Corticosteroids for Ophthalmic Injection (Dextenza,
Iluvien, Ozurdex, Retisert, Xipere, Yutiq)
Reference Number: CP.PHAR.385
Effective Date: 09.01.18
Last Review Date: 08.25
Line of Business: Commercial, HIM, Medicaid

Coding Implications
Revision Log

See [Important Reminder](at the end of this policy for important regulatory and legal
information.

Description

The following are corticosteroids for ophthalmic injection requiring prior authorization:

• dexamethasone intravitreal implant (Ozurdex®), dexamethasone ophthalmic insert (Dextenza®),
• fluocinolone acetonide intravitreal implant (Iluvien®, Retisert®, Yutiq®), and triamcinolone
  acetonide suprachoroidal injection (Xipere®).

FDA Approved Indication(s)

Dextenza is indicated for the treatment of:

• Ocular inflammation and pain following ophthalmic surgery in adults and pediatric patients
• Ocular itching associated with allergic conjunctivitis in adults and pediatric patients aged 2
  years and older

Iluvien is indicated for the treatment of:

• Diabetic macular edema in patients who have been previously treated with a course of
  corticosteroids and did not have a clinically significant rise in intraocular pressure
• Chronic non-infectious uveitis affecting the posterior segment of the eye

Ozurdex is indicated for the treatment of:

• Macular edema following branch retinal vein occlusion (BRVO) or central retinal vein
  occlusion (CRVO)
• Non-infectious uveitis affecting the posterior segment of the eye
• Diabetic macular edema (DME)

Retisert and Yutiq are indicated for the treatment of chronic non-infectious uveitis affecting the
posterior segment of the eye.

Xipere is indicated for the treatment of macular edema associated with uveitis.

Limitations of use: The use of Dextenza is not recommended for the treatment of ocular itching
associated with allergic conjunctivitis in pediatric patients who require sedation for the insertion
procedure.

Policy/Criteria

Approval duration:
Ozurdex, Iluvien, Retisert, Yutiq, Xipere – 3 months (one implant or injection per eye)
Dextenza – 1 month (one insert per eye)

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CLINICAL POLICY
Corticosteroids for Ophthalmic Injection

B. Other diagnoses/indications (must meet 1 or 2):

1. If this drug has recently (within the last 6 months) undergone a label change (e.g.,
   newly approved indication, age expansion, new dosing regimen) that is not yet
   reflected in this policy, refer to one of the following policies (a or b):
   a. For drugs on the formulary (commercial, health insurance marketplace) or PDL
   (Medicaid), the no coverage criteria policy for the relevant line of business:
   CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and
   CP.PMN.255 for Medicaid; or
   b. For drugs NOT on the formulary (commercial, health insurance marketplace) or
   PDL (Medicaid), the non-formulary policy for the relevant line of business:
   CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and
   CP.PMN.16 for Medicaid; or
2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed
   under section III (Diagnoses/Indications for which coverage is NOT authorized) AND
   criterion 1 above does not apply, refer to the off-label use policy for the relevant line
   of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance
   marketplace, and CP.PMN.53 for Medicaid.

III. Diagnoses/Indications for which coverage is NOT authorized:

A. Non-FDA approved indications, which are not addressed in this policy, unless there is

sufficient documentation of efficacy and safety according to the off label use policies –
CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and
CP.PMN.53 for Medicaid, or evidence of coverage documents.

IV. Appendices/General Information

Appendix A: Abbreviation/Acronym Key

BRVO: branch retinal vein occlusion
CRVO: central retinal vein occlusion
DME: diabetic macular edema

Appendix B: Therapeutic Alternatives

This table provides a listing of preferred alternative therapy recommended in the approval
criteria. The drugs listed here may not be a formulary agent for all relevant lines of business
and may require prior authorization.

| Drug Name | Dosing Regimen | Dose Limit/

Maximum Dose |

|---|---|---|

| anti-VEGF agents (e.g.,

bevacizumab, Lucentis®,
Eylea®, Vabysmo®, Beovu®) | Macular Edema
Refer to prescribing information | Refer to
prescribing
information |

| systemic corticosteroids (e.g.,

prednisone) | Uveitis
prednisone 5 – 60 mg/day PO in 1
– 4 divided doses | Varies |

| non-biologic systemic

immunosuppressive therapy
(e.g., azathioprine, Leukeran®) | Uveitis
Varies | Varies |

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CLINICAL POLICY
Corticosteroids for Ophthalmic Injection

| Drug Name | Dosing Regimen | Dose Limit/

Maximum Dose |

|---|---|---|

| [chlorambucil]†,

cyclophosphamide†,
cyclosporine [Sandimmune®,
Neoral®], methotrexate
[Trexall®], mycophenolate
mofetil [Cellcept®], tacrolimus
[Prograf®]) | | |

| topical dual-acting mast cell

stabilizer/antihistamine (e.g.,
azelastine, bepotastine,
epinastine, ketotifen,
olopatadine) | Allergic Conjunctivitis
1 to 2 drops in affected eye(s) per
day | Varies |

| topical mast cell stabilizer (e.g.,

cromolyn, lodoxamide,
nedocromil) | Allergic Conjunctivitis
2 to 6 drops in affected eye(s) per
day | Varies |

| topical antihistamine (e.g.,

alcaftadine, emedastine) | Allergic Conjunctivitis
1 to 4 drops in affected eye(s) per
day | Varies |

| topical corticosteroids (e.g.,

loteprednol, dexamethasone) | Allergic Conjunctivitis or Ocular
Pain and Inflammation
Loteprednol: 1 to 2 drops in
affected eye(s) QID
Dexamethasone: 1 to 2 drops in
affected eye(s) up to every hour for
severe disease | Varies |

† Off-label
Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only
and generic name® when the drug is available by both brand and generic.

Appendix C: Contraindications / Boxed Warnings

• Contraindication(s):
  
  • Dextenza: active corneal, conjunctival or canalicular infections, including epithelial
    herpes simplex keratitis (dendritic keratitis), vaccinia, varicella; mycobacterial
    infections; fungal diseases of the eye, and dacryocystitis.
  • Retisert: patients with active viral diseases of the cornea and conjunctiva including
    epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and
    also in active bacterial, mycobacterial or fungal infections of the eye.
  • Iluvien, Ozurdex, Xipere, Yutiq: patients with active or suspected ocular or periocular
    infections including most viral disease of the cornea and conjunctiva including active
    epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella,
    mycobacterial infections and fungal disease.
  • Iluvien, Ozurdex: patients with glaucoma with cup to disc rations of greater than 0.8
  • Ozurdex: patients with posterior lens capsules that is torn or ruptured because of the
    risk of migration into the anterior chamber.

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• Iluvien, Ozurdex, Yutiq, Xipere: hypersensitivity.
  
  • Boxed warning(s): none reported

Appendix D: General Information

• Based on clinical trials with Retisert:
  
  • Within 3 years post-implantation, approximately 77% of patients will require
    intravitreal pressure (IOP) lowering medications to control intraocular pressure and
    37% of patients will require filtering procedures to control intraocular pressure.
  • Following implantation of Retisert, nearly all patients will experience an immediate
    and temporary decrease in visual acuity in the implanted eye which lasts for
    approximately one to four weeks post-operatively.
  • During the 3-year post-implantation period, nearly all phakic eyes are expected to
    develop cataracts and require cataract surgery.
• In one study, intravitreal bevacizumab (1.25 mg) and the dexamethasone (DEX) (0.7 mg)
  implant were compared in a randomized, Phase II trial called the BEVORDEX study. 79
  Forty-two eyes received intravitreal bevacizumab every 4 weeks, and 46 eyes received an
  intravitreal DEX (0.7 mg) implant every 16 weeks, PRN) regimen for 12 months. The primary outcome of the study was to gain ten or more letters
  in the best-corrected distance visual acuity (BCVA) at 12 months, which was achieved in
  40% of the bevacizumab-treated eyes and 41% of the DEX implant-treated group (P =
  0.99). The mean corneal refractive therapy (CRT) decrease was statistically significant
  between the groups, and the reduction was 122 µm in the bevacizumab group and 187
  µm in the DEX implant group (P=0.015). The mean number of injections over 1 year was
  8.6 for the bevacizumab group and 2.7 for the DEX implant group. Finally, in the DEX
  implant-treated eyes, 11% lost ten or more letters of the BCVA, which was due to
  cataracts in 4 of 5 cases; none lost ten letters in the bevacizumab-treated eyes.
• The Chart Review of Ozurdex in Macular Edema (CHROME) study evaluated the real-
  world use, efficacy, and safety of one or more dexamethasone intravitreal implant(s) 0.7
  mg (DEX implant) in 120 eyes with macular edema (ME). The mean number of DEX
  implant injections was 1.7 ± 0.1 in all study eyes; 44.2% of eyes had repeat DEX implant
  injections (reinjection interval 2.3-4.9 months).
• According to Pommier et al., an average of 2.6 injections of Ozurdex were needed to
  obtain a 58.6% of patients who gained more than 15 letters, and 51.1% of patients showed
  macular edema resolution.
• The POINT trial by Thorne et al. found no significant difference between intravitreal
  triamcinolone acetonide injection and intravitreal dexamethasone implant in terms of
  safety and efficacy for the treatment of uveitic macular edema.

V. Dosage and Administration

inflammation and
pain after
surgery, ocular
itching associated | Insert into the lower lacrimal
punctum and into the
canaliculus. A single
insert releases a 0.4 mg dose
of dexamethasone for up
to 30 days following insertion | 1 insert per eye
per 30 days |

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CLINICAL POLICY
Corticosteroids for Ophthalmic Injection

0.7 mg dexamethasone
intravitreally | One implant
injection per eye
every 6 months |

| Fluocinolone

(Iluvien) | DME, uveitis | Inject the implant containing
0.19 mg fluocinolone
intravitreally | DME: One
implant injection
per eye every 12
months
Uveitis: One
implant injection
per eye every 36
months |

| Fluocinolone

(Retisert) | Uveitis | Inject the implant containing
0.59 mg fluocinolone
intravitreally | One implant
injection per eye
every 30 months |

| Fluocinolone

(Yutiq) | Uveitis | Inject the implant containing
0.18 mg fluocinolone
intravitreally | One implant
injection per eye
every 36 months |

| Triamcinolone

(Xipere) | Macular edema
associated with
uveitis | 4 mg (0.1 mL) administered
as a suprachoroidal injection | One injection per
eye every 12
weeks |

VI. Product Availability

CLINICAL POLICY

Corticosteroids for Ophthalmic Injection

Important Reminder

This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable.

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