Byooviz

BYOOVIZ- ranibizumab injection, solution
BIOGEN INC.

1 INDICATIONS AND USAGE

BYOOVIZ is indicated for the treatment of patients with:

1.1 Neovascular (Wet) Age-Related Macular Degeneration (AMD)

1.2 Macular Edema Following Retinal Vein Occlusion(RVO)

1.3 Myopic Choroidal Neovascularization (mCNV)

2 DOSAGE AND ADMINISTRATION

2.1 General Dosing Information

FOR OPHTHALMIC INTRAVITREAL INJECTION.

Vials: A 5-micron sterile filter needle (19-gauge × 1-1/2 inch), a 1-mL Luer lock syringe and a 30- gauge × ½ inch sterile injection needle are needed but not included.

2.2 Neovascular (Wet) Age-Related Macular Degeneration (AMD)

BYOOVIZ 0.5 mg (0.05 mL of 10 mg/mL solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days).

Although not as effective, patients may be treated with 3 monthly doses followed by less frequent dosing with regular assessment. In the 9 months after three initial monthly doses, less frequent dosing with 4-5 doses onaverage is expected to maintain visual acuity while monthly dosing may be expected to result in an additional average 1-2 letter gain. Patients should be assessed regularly [see Clinical Studies (14.1) ].

Although not as effective, patients may also be treated with one dose every 3 months after 4 monthly doses. Compared with continued monthly dosing, dosing every 3 months over the next 9 months will lead to an approximate 5-letter (1-line) loss of visual acuity benefit, on average. Patients should be assessed regularly [see Clinical Studies (14.1) ].

2.3 Macular Edema Following Retinal Vein Occlusion (RVO)

BYOOVIZ 0.5 mg (0.05 mL of 10 mg/mL solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days).

In Studies RVO-1 and RVO-2, patients received monthly injections of ranibizumab for 6 months. In spite of being guided by optical coherence tomography and visual acuity re-treatment criteria, patients who were then not treated at Month 6 experienced on average, a loss of visual acuity at Month 7, whereas patients who were treated at Month 6 did not. Patients should be treated monthly [see Clinical Studies (14.2) ].

2.4 Myopic Choroidal Neovascularization (mCNV)

BYOOVIZ 0.5 mg (0.05 mL of 10 mg/mL BYOOVIZ solution) is recommended to be initially administered by intravitreal injection once a month (approximately 28 days) for up to 3 months. Patients may be retreated if needed [see Clinical Studies (14.3) ].

2.5 Preparation for Administration

Vial:

Using aseptic technique, all of the BYOOVIZ vial contents are withdrawn through a 5-micron (19- gauge × 1-1/2 inch), sterile filter needle attached to a 1 mL syringe (not included). The filter needle should be discarded after withdrawal of the vial contents and should not be used for intravitreal injection. The filter needle should be replaced with a sterile 30-gauge × ½ inch needle for the intravitreal injection.

Use aseptic technique to carry out the following preparation steps:

1. Prepare for intravitreal injection with the following medical devices for single use (not included):
   • a 5-micron sterile filter needle (19-gauge × 1-1/2 inch)
   • a 1 mL sterile Luer lock syringe (with marking to measure 0.05 mL)
   • a sterile injection needle (30-gauge × 1/2-inch)
2. Before withdrawal, disinfect the outer part of the rubber stopper of the vial.
3. Place a 5-micron filter needle (19-gauge × 1-1/2 inch) onto a 1 mL Luer lock syringe using aseptic technique.
4. Push the filter needle into the center of the vial stopper until the needle touches the bottom edge of the vial.
5. Withdraw all the liquid fromthe vial, keeping the vial in an upright position, slightly inclined to ease complete withdrawal.
   

   

6. Ensure that the plunger rod is drawn sufficiently backwhen emptying the vial in order to completely empty the filter needle.
   

   

7. The filter needle should be discarded after withdrawal of the vial contents and must not be used for the intravitreal injection.
8. Attach a 30-gauge × 1/2-inch sterile injection needle firmly onto the syringe by screwing it tightly onto the Luer lock. Carefully remove the needle cap by pulling it straight off. Do not wipe the needle at any time.
   

   

9. Hold the syringe with the needle pointing up. If there are any air bubbles, gently tap the syringe with your finger until the bubbles rise to the top.
   

   

10. Hold the syringe at eye level, and carefully push the plunger rod until the plunger tip is aligned with the line that marks 0.05 mL on the syringe.

    

FigureFigureFigureFigureFigure

2.6 Administration

The intravitreal injection procedure should be carried out under controlled aseptic conditions, which include the use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent).

Adequate anesthesia and a broad-spectrum microbicide should be given prior to the injection.

Prior to and 30 minutes following the intravitreal injection, patients should be monitored for elevation in intraocular pressure using tonometry. Monitoring may also consist of a check for perfusion of the optic nerve head immediately after the injection [see Warnings and Precautions (5.2) ]. Patients should also be monitored for and instructed to report any symptoms suggestive of endophthalmitis without delay following the injection [see Warnings and Precautions (5.1) ].

Each vial should only be used for the treatment of a single eye. If the contralateral eye requires treatment, a new vial should be used and the sterile field, syringe, gloves, drapes, eyelid speculum, filter needle (vial only), and injection needles should be changed before BYOOVIZ is administered to the other eye.

No special dosage modification is required for any of the populations that have been studied (e.g., gender, elderly).

3 DOSAGE FORMS AND STRENGTHS

Single-dose glass vial designed to provide 0.05 mL for intravitreal injection. Clear to slightly opalescent and colorless to pale yellow, 10 mg/mL solution.

4 CONTRAINDICATIONS

4.1 Ocular or Periocular Infections

BYOOVIZ is contraindicated in patients with ocular or periocular infections.

4.2 Hypersensitivity

BYOOVIZ is contraindicated in patients with known hypersensitivity to ranibizumab products or any of the excipients in BYOOVIZ. Hypersensitivity reactions may manifest as severe intraocular inflammation.

5 WARNINGS AND PRECAUTIONS

5.1 Endophthalmitis and Retinal Detachments

Intravitreal injections, including those with ranibizumab products, have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique should always be used when administering BYOOVIZ. In addition, patients should be monitored following the injection to permit early treatment should an infection occur [see Dosage and Administration (2.5, 2.6) and Patient Counseling Information (17)].

5.2 Increases in Intraocular Pressure

Increases in intraocular pressure have been noted both pre-injection and post-injection (at 60 minutes) while being treated with ranibizumab products. Monitor intraocular pressure prior to and following intravitreal injection with BYOOVIZ and manage appropriately [see Dosage and Administration (2.6) ].

5.3 Thromboembolic Events

Although there was a low rate of arterial thromboembolic events (ATEs) observed in the ranibizumab clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. Arterial thromboembolic events are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).

Neovascular (Wet) Age-Related Macular Degeneration

The ATE rate in the three controlled neovascular AMD studies (AMD-1, AMD-2, AMD-3) during the first year was 1.9% (17 of 874) in the combined group of patients treated with 0.3 mg or 0.5 mg ranibizumab compared with 1.1% (5 of 441) in patients from the control arms [see Clinical Studies (14.1) ]. In the second year of Studies AMD-1 and AMD-2, the ATE rate was 2.6% (19 of 721) in the combined group of ranibizumab-treated patients compared with 2.9% (10 of 344) in patients from the control arms. In Study AMD-4, the ATE rates observed in the 0.5 mg arms during the first and second year were similar to rates observed in Studies AMD-1, AMD-2, and AMD-3.

In a pooled analysis of 2-year controlled studies [AMD-1, AMD-2, and a study of ranibizumab used adjunctively with verteporfin photodynamic therapy (PDT)], the stroke rate (including both ischemic and hemorrhagic stroke) was 2.7% (13 of 484) in patients treated with 0.5 mg ranibizumab compared to 1.1% (5 of 435) in patients in the control arms [odds ratio 2.2 (95% confidence interval (0.8-7.1)].

Macular Edema Following Retinal Vein Occlusion

The ATE rate in the two controlled RVO studies during the first 6 months was 0.8% in both the ranibizumab and control arms of the studies (4 of 525 in the combined group of patients treated with 0.3 mg or 0.5 mg ranibizumab and 2 of 260 in the control arms) [see Clinical Studies (14.2) ]. The stroke rate was 0.2% (1 of 525) in the combined group of ranibizumab -treated patients compared to 0.4% (1 of 260) in the control arms.