Faricimab is a vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) inhibitor indicated for the treatment of adults with neovascular (wet) age-related macular degeneration (nAMD), diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO). The drug is administered via intravitreal injection at an initial dosing frequency of every 4 weeks. After the initial doses, the dosing frequency may be extended based on the individual patient response. Treatment may be associated with increased intraocular pressure, endophthalmitis, retinal detachment, and arterial thromboembolic events (ATEs). Instruct patients to immediately report any symptoms of endophthalmitis or retinal detachment (e.g., vision loss, eye pain, redness of the eye, photophobia, blurred vision) to their health care provider. Faricimab is contraindicated for use in patients with ocular or periocular infections and patients with active intraocular inflammation.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Faricimab solution should be clear to opalescent and colorless to brownish-yellow. Do not use if particulates, cloudiness, or discoloration are visible. Do not use if packaging, vial, or transfer filter needle are expired, damaged, or have been tampered with.
Other Injectable Administration
Intravitreal Administration
Preparation:
-Ensure aseptic technique is used when preparing the dose.
-Gather the following supplies:
--Kit containing the faricimab single-use glass vial and single use 5-micron blunt, 18-gauge x 1.5 inch transfer filter needle.
-Sterile 1 mL Luer lock syringe with 0.05 mL dose mark.
-Sterile 30-gauge x 0.5 inch injection needle. Note: A 30-gauge needle is recommended to avoid increased injection force.
-Alcohol swab.
-Remove the faricimab vial from the refrigerator and allow the vial to reach room temperature of 20 to 25 degrees C (68 to 77 degrees F). The vial may be kept at room temperature for up to 24 hours. The vial should remain in the original carton to protect it from light. Do not shake the vial.
-Place the vial upright on a flat surface for about 1 minute after removal from the packaging. Ensure all liquid settles to the bottom of the vial by gently tapping the vial with a finger.
-Remove the flip-off cap from the vial and wipe the septum with an alcohol swab.
-Firmly attach the included 18-gauge x 1.5 inch transfer filter needle onto a 1 mL Luer lock syringe.
-Push the transfer filter needle into the center of the vial septum. Tilt the vial slightly and push the needle all the way in until it touches the bottom edge of the vial.
-While holding the vial slightly inclined, slowly withdraw all the liquid from the vial. Avoid adding air into the syringe by keeping the bevel of the needle submerged in the liquid.
-Draw the plunger rod sufficiently back to completely empty the transfer filter needle.
-Disconnect and discard the transfer filter needle. DO NOT use this needle for the intravitreal injection.
-Firmly attach a 30-gauge x 0.5 inch injection needle onto the Luer lock syringe.
-Hold the syringe with the needle pointing up and check for air bubbles. If present, gently tap the syringe with a finger until the bubbles rise to the top.
-Expel any air from the syringe and needle, and depress the plunger to align the rubber stopper tip to the 0.05 mL dose mark.
-Administer the injection immediately after preparation of the dose.
Intravitreal Injection
-The injection must be carried out under aseptic conditions, which includes use of surgical hand disinfection, sterile gloves, a sterile drape and a sterile eyelid speculum (or equivalent), and the availability of sterile paracentesis equipment (if required).
-Prior to the injection, administer adequate anesthesia and a broad-spectrum microbicide.
-Inject slowly until the rubber stopper reaches the end of the syringe to deliver the 0.05 mL volume.
-Confirm delivery of the full dose by checking that the rubber stopper has reached the end of the syringe barrel.
-Immediately after the injection, monitor for elevation in intraocular pressure. Monitoring may consist of a check for perfusion of the optic nerve head or tonometry. If required, a sterile paracentesis needle should be available.
-Instruct the patient to promptly report any symptoms suggestive of endophthalmitis or retinal detachment (e.g., vision loss, ocular pain, eye redness, photophobia, blurred vision).
-Each syringe should only be used to treat a single eye. If the contralateral eye requires treatment, a new syringe should be used and the sterile field, syringe, gloves, drapes, eyelid speculum, and filter and injection needles should be changed.
-Appropriately discard any unused medicinal product or waste material.
Safety data for faricimab is available from four Phase 3 trials involving a total of 1,926 drug recipients [1,262 patient with diabetic macular edema (DME) and 664 patients with age-related macular degeneration (AMD)]. The most commonly reported adverse events included cataracts (3% to 15%), conjunctival hemorrhage (7% to 8%), vitreous floaters (3% to 4%), retinal pigment epithelial tear (3%), ocular hypertension or increased intraocular pressure (3% to 4%), ocular pain (3%), ocular inflammation (1% to 2%; includes iridocyclitis, iritis, uveitis, vitritis), increased lacrimation (1%), and ocular irritation or discomfort (up to 1%). Other ophthalmic adverse events reported in less than 1% of drug recipients included corneal abrasion, ocular pruritus, ocular hyperemia, blurred vision, foreign body sensation, endophthalmitis, transient visual impairment or reduced visual acuity, vitreous or ocular hemorrhage, retinal tear, and rhegmatogenous retinal detachment.
Antibody formation to faricimab may occur due to an immune response. Pretreatment incidence of anti-faricimab antibodies was approximately 1.8% and 0.8% in age-related macular degeneration (AMD) and diabetic macular edema (DME) patients, respectively. After starting treatment, anti-faricimab antibodies were detected in 10.4% of AMD patients and 8.4% of DME patients. The detection of an immune response is highly dependent on the sensitivity and specificity of the assay used, sample handling, timing of sample collection, concurrent medications, and underlying disease. For these reasons, comparison with other products may be misleading.
Intravitreal use of vascular endothelial growth factor (VEGF) inhibitors, such as faricimab, may be associated with arterial thromboembolic events (ATE) such as thromboembolism, nonfatal stroke, nonfatal myocardial infarction, and vascular death. During the first year of faricimab treatment for age-related macular degeneration (AMD) in clinical trials, 1% (n = 7 of 664) of faricimab patients reported an ATE as compared with 1% (n = 6 of 662) of patients treated with aflibercept. In diabetic macular edema (DME) clinical trials, ATEs were reported in 5% (n = 64 of 1,262) of faricimab patients and 5% (n = 32 of 625) of patients receiving aflibercept during the first year of treatment.
During postmarketing, retinal vasculitis with or without retinal vascular occlusion has been reported following the use of faricimab; it was typically associated with intraocular inflammation.
Faricimab is contraindicated for use in patients with a periocular or ocular infection. Cases of endophthalmitis have been reported with the intravitreal injections. To limit the risk of infection, ensure proper aseptic technique is used during preparation and administration of the dose; this includes use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent). Additionally, a broad-spectrum ocular microbicide should be given prior to the intravitreal injection. Patients should be monitored to permit early treatment should an infection occur. Instruct patients to immediately report any signs or symptoms that could be associated with an infection (e.g., vision loss, pain, redness, sensitive to light, decreased visual acuity).
Faricimab is contraindicated for use in patients with active intraocular inflammation. The drug is also contraindicated for use in patients with hypersensitivity to faricimab or to any of the components of the product. Hypersensitivity reactions may manifest as severe intraocular inflammation, rash, pruritus, urticaria, or erythema.
Treatment with faricimab has been associated with endophthalmitis, retinal tears and rhegmatogenous retinal detachment. Patients should be monitored to permit early treatment should retinal detachment occur. Instruct patients to immediately report any signs or symptoms (e.g., vision loss, decreased visual acuity) that could be associated with these events.
Transient increased intraocular pressure (IOP) has been observed within 60 minutes of faricimab intravitreal injection. Use with caution in patients with a history of glaucoma. Monitor patients for elevations in intraocular pressure immediately following the intravitreal injection. Appropriate monitoring may consist of a check for perfusion of the optic nerve head or tonometry. If required, a sterile paracentesis needle should be available. Instruct patients to seek immediate care with their ophthalmologist if the treated eye(s) becomes red, sensitive to light, painful, or develops a change in vision.
Caution is warranted when administering faricimab to high risk patients, including patients with a history of thromboembolic disease. Vascular endothelial growth factor (VEGF) has been shown to be an important component in the development of collateral vessels in ischemic heart disease. Inhibition of VEGF by faricimab could increase the risk for arterial thromboembolic events (ATEs), including nonfatal stroke, nonfatal myocardial infarction, or vascular death. During faricimab clinical trials, 1% of age-related macular degeneration patients (n = 7 of 664), 5% of diabetic macular edema patients (n = 64 of 1,262), and retinal vein occlusion 1.1% (n = 7 of 641) reported an ATE from baseline to week 100 of treatment with faricimab.
Patients may experience temporary visual disturbance after receiving the faricimab intravitreal injection. Instruct patients to avoid driving or operating machinery until their vision has sufficiently recovered.
Do not administer faricimab during pregnancy unless the potential benefit to the patient outweighs the potential risk to the fetus. No adequate and well-controlled studies regarding the use of faricimab during human pregnancy have been conducted; however, based on the mechanism of action, there is a potential risk to embryo-fetal development and female reproductive capacity. In animal studies, an increased incidence of abortions was observed in pregnant cynomolgus monkeys who received 5 weekly intravenous doses of 1 or 3 mg/kg starting on day 20 of gestation. The maximum plasma concentration (Cmax) produced by the 1 mg/kg intravenous dose was 158-times the human exposure at the maximum recommended intravitreal dose of 6 mg once every 4 weeks.
Counsel patients on the reproductive risk and contraception requirements associated with faricimab therapy. Based on the mechanism of action [i.e., inhibition of vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang-2)], faricimab treatment may pose a risk to embryo-fetal development and reproductive capacity; however, no studies have been conducted to associate use of the drug with human infertility. Patients of reproductive potential should use effective contraception prior to the initial dose, during treatment, and for at least 3 months after the last dose.
There are no data available on the presence of faricimab in human milk, the effects on a breast-fed infant, or the effects on milk production. Because many drugs are excreted in breast milk and the potential for absorption and fetal harm exists, use caution when administering faricimab to a lactating mother. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for faricimab and any potential adverse effects on the breast-fed infant from exposure to the drug.
Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of faricimab. Patients who develop these events should discontinue treatment with faricimab and report any changes in vision without delay.
For the treatment of neovascular (wet) age-related macular degeneration (nAMD):
Intravitreal dosage:
Adults: 6 mg by intravitreal injection every 4 weeks (approximately every 28 +/- 7 days) for the first 4 doses, then perform optical coherence tomography and visual acuity evaluations 8 and 12 weeks after the fourth dose. Based on the results of these evaluations, subsequent 6 mg intravitreal injections may be given using 1 of the following 3 regimens: (1) Weeks 28 and 44; (2) Weeks 24, 36, 48; or (3) Weeks 20, 28, 36, 44. Although additional efficacy was not demonstrated in most patients when faricimab was administered every 4 weeks compared to every 8 weeks, some patients may still require every 4 week dosing after receipt of the initial 4 doses. Patients should be assessed regularly.
For the treatment of diabetic macular edema:
Intravitreal dosage:
Adults: 6 mg by intravitreal injection in the affected eye(s) every 4 weeks for at least 4 doses. If after at least 4 doses, resolution of edema based on the central subfield thickness (CST) of the macula as measured by optical coherence tomography is achieved, then the dosing interval may be modified by extensions of up to 4 week increments or reductions of up to 8 week increments based on CST and visual acuity evaluations. Alternatively, 6 mg by intravitreal injection in the affected eye(s) every 4 weeks for the first 6 doses, followed by 6 mg every 8 weeks. Although additional efficacy was not demonstrated in most when faricimab was administered every 4 weeks compared to every 8 weeks, some may still require every 4 week dosing after receipt of the initial doses. Guidelines recommend intravitreous agents with anti-vascular endothelial growth factor activity, such as faricimab, as first-line therapies for the management of central-involved diabetic macular edema.
For the treatment of macular edema following retinal vein occlusion:
Intravitreal dosage:
Adults: 6 mg by intravitreal injection every 4 weeks (approximately every 28 +/- 7 days, monthly) for 6 months.
Maximum Dosage Limits:
-Adults
6 mg intravitreally per affected eye.
-Geriatric
6 mg intravitreally per affected eye.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Faricimab products.
Faricimab is a humanized bispecific immunoglobulin G1 (IgG1) antibody that binds to vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang-2). By binding to and inhibiting VEGF-A, faricimab suppresses endothelial cell proliferation, neovascularization, and vascular permeability. By inhibiting Ang-2, faricimab promotes vascular stability and desensitizes blood vessels to the effects of VEGF-A. It has been noted that Ang-2 levels are increased in some patients with neovascular (wet) age-related macular degeneration (AMD) and diabetic macular edema (DME); however, the contributions of Ang-2 inhibition to the treatment effect and clinical response has not yet been established.
Faricimab is administered by intravitreal injection. The metabolism and elimination of faricimab has not been completely identified; however, the drug is expected to be catabolized by lysosomes into small peptides and amino acids, which may be excreted renally. This is a similar metabolic and elimination pathway as endogenous IgG. The estimated mean apparent systemic half-life of faricimab is 7.5 days.
Affected cytochrome P450 isoenzymes: none
-Route-Specific Pharmacokinetics
Other Route(s)
Intravitreal Route
Maximum faricimab plasma concentrations (Cmax) are estimated to occur approximately 2 days post-dose. The estimated mean free drug (i.e., unbound to VEGF-A and Ang-2) plasma Cmax in age-related macular degeneration (AMD) and diabetic macular edema (DME) patients are 0.23 mcg/mL and 0.22 mcg/mL, respectively. After repeated intravitreal injections, mean plasma free faricimab trough concentrations (Cmin) are predicted to be 0.002 to 0.003 mcg/mL with an every 8 week dosing interval. No drug accumulation is expected in the vitreous or plasma after repeated intravitreal doses.
-Special Populations
Hepatic Impairment
The effects of any degree of hepatic impairment on the pharmacokinetics of faricimab are unknown.
Renal Impairment
The systemic pharmacokinetics of faricimab are not influenced by mild to severe renal impairment (i.e., CrCl 15 to 89 mL/minute). The effects of severe renal impairment (i.e., CrCl less than 15 mL/minute) on the pharmacokinetics of faricimab are unknown.
Gender Differences
The systemic pharmacokinetics of faricimab are not influenced by gender.
Ethnic Differences
The systemic pharmacokinetics of faricimab are not influenced by ethnicity.