ADVERSE REACTIONS SECTION.

6ADVERSE REACTIONS. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reactions (incidence 2%) were transient blurred vision, reduced visual acuity, photophobia, and mild eye discomfort.. Most common ocular adverse reactions include transient blurred vision, reduced visual acuity, photophobia, superficial punctate keratitis, and mild eye discomfort. Increased intraocular pressure has been reported following the use of mydriatics (6.1)Systemic adverse reactions including dryness of the mouth, tachycardia, headache, allergic reactions, nausea, vomiting, pallor, central nervous system disturbances and muscle rigidity have been reported with the use of tropicamide (6.2)To report SUSPECTED ADVERSE REACTIONS, contact Eyenovia, Inc. at 1-833-393-6684 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Most common ocular adverse reactions include transient blurred vision, reduced visual acuity, photophobia, superficial punctate keratitis, and mild eye discomfort. Increased intraocular pressure has been reported following the use of mydriatics (6.1). Systemic adverse reactions including dryness of the mouth, tachycardia, headache, allergic reactions, nausea, vomiting, pallor, central nervous system disturbances and muscle rigidity have been reported with the use of tropicamide (6.2). 6.1Ocular Adverse Reactions. Transient blurred vision, reduced visual acuity, photophobia, superficial punctate keratitis, and mild eye discomfort may occur. Increased intraocular pressure has been reported following the use of mydriatics.. 6.2Systemic Adverse Reactions. Dryness of the mouth, tachycardia, headache, allergic reactions, nausea, vomiting, pallor, central nervous system disturbances and muscle rigidity have been reported with the use of tropicamide. Psychotic reactions, behavioral disturbances, and vasomotor or cardiorespiratory collapse in children have been reported with the use of anticholinergic drugs.A marked increase in blood pressure has been reported with the use of phenylephrine, particularly, but not limited to, low weight premature neonates, infants, and hypertensive patients.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1Mechanism of Action. Tropicamide, the anticholinergic component of MYDCOMBI, blocks the responses of the sphincter muscle of the iris, dilating the pupil (mydriasis). Phenylephrine hydrochloride, the alpha-1 adrenergic agonist component of MYDCOMBI, acts as mydriatic agent by contracting the dilator muscle of the iris.. 12.2Pharmacodynamics. MYDCOMBI acts in 15 to 30 minutes with maximal mydriasis occurring in 20 to 90 minutes. Darker irides tend to dilate slower than lightly pigmented irides and to achieve maximal effect may require more doses than lighter irides.Mydriasis will reverse spontaneously with time, with recovery after to hours. Complete recovery from mydriasis in some individuals may require 24 hours.

CLINICAL STUDIES SECTION.

13CLINICAL STUDIES. Two Phase clinical trials were conducted to evaluate the efficacy of MYDCOMBI for achievement of mydriasis. The MIST-1 study was prospective, double-masked, active-controlled, 3-period cross-over, superiority study to compare the pupil dilating effect of MYDCOMBI to tropicamide 1% and to phenylephrine 2.5%, with all solutions topically administered by the Optejet(R) Dispenser (N 64 subjects; 128 eyes). The MIST-2 study was prospective, multicenter, double-masked, placebo-controlled, 3-period crossover, superiority study to compare the pupil dilating effect of MYDCOMBI to placebo (eyewash solution), with both solutions topically administered by the Optejet Dispenser (N 70 subjects; 140 eyes).The primary efficacy endpoint for both studies was the mean change in 35-minute pupil diameter compared to baseline as measured by digital pupillometry in highly photopic conditions. Data from the studies are presented in Table 1. At 35 minutes post-dose, the mean change in pupil diameter was 4.7 mm with MYDCOMBI, 4.1 mm with tropicamide, and 0.9 mm with phenylephrine in MIST-1, and was 4.8 mm with MYDCOMBI and 0.1 mm with placebo in MIST-2. MYDCOMBI was statistically superior to tropicamide administered alone and phenylephrine administered alone.Table Pupil Size and Change in Diameter from Baseline at 35 Minutes Post-Dose (MIST-1 and MIST-2) (Per-Protocol Population The per-protocol (PP) population included all randomized subjects who received at least one dose of study medication and completed all planned assessments (related to the primary endpoint) without major protocol violations. Two subjects in MIST-1 and one subject in MIST-2 who withdrew consent after their first treatment visit were not included in the PP populations which resulted in 62 completed subjects (124 eyes) in MIST-1 and 69 completed subjects (138 eyes) in MIST-2 comprised the PP populations. Sensitivity analysis performed on the intent-to-treat (ITT) population including all randomized subjects resulted in consistent efficacy results. )MIST-1MIST-2VisitMYDCOMBI(N 124)Tropicamide Alone(N 124)Phenylephrine Alone(N 124)MYDCOMBI(N 138)Placebo(N 138)SD=Standard DeviationMean Baseline (SD)2.6 (0.05)2.6 (0.05)2.6 (0.05)2.6 (0.04)2.6 (0.04)35-Minutes Post-Dose (SD)7.3 (0.08)6.7 (0.08)3.5 (0.08)7.3 (0.07)2.7 (0.05)Change from Baseline (SD)4.7 (0.07)4.1 (0.06)0.9 (0.08)4.8 (0.07)0.1 (0.04)Difference from MYDCOMBI(95% CI) Treatment differences and 95% confidence interval estimates were based on mixed model including treatment, eye, baseline diameter, and carryover effect (for MIST-2 study only). In both studies, an unstructured covariance structure was used to account for within-subject correlation between eyes. --0.6(0.4, 0.8)3.9(3.7, 4.1)--4.7(4.5, 4.8)MYDCOMBI provided clinically significant effect in the proportion of eyes achieving pupil diameter of >= mm at 35-minute post-dose in 94% of eyes compared to 78% of eyes administered tropicamide alone and 1.6% of eyes administered phenylephrine alone, and 0% of eyes administered placebo. As shown in Figure 2, peak effect was measured at the 80-minute evaluation when the mean change from baseline was 5.2 mm. Treatment differences in mydriasis were observed as early as 20 minutes and still present at 180 minutes post-dose, the end of the protocol-specified observation period.Figure 2: MIST-1 and MIST-2 pooled, mean pupil diameter vs measurement time, by treatment group. Vertical bars show 95% confidence interval for the mean at each point. Smooth curves are based on an degrees of freedom (df) generalized additive model (GAM) smooth through time, adjusting for baseline pupil diameter. Confidence intervals are not adjusted for correlation.. Figure 2.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. Known hypersensitivity to any component of the formulation (4.1). Known hypersensitivity to any component of the formulation (4.1). 4.1Known Hypersensitivity. Contraindicated in persons showing known hypersensitivity to any component of the formulation.

DESCRIPTION SECTION.

11DESCRIPTION. MYDCOMBI is sterile, clear, colorless fixed dose combination of an anticholinergic (tropicamide) and an alpha-adrenergic receptor agonist (phenylephrine hydrochloride) for topical ophthalmic use. The active ingredients are represented by the chemical structures below.Tropicamide:Chemical Name: Benzeneacetamide, N-ethyl--(hydroxymethyl)-N-(4-pyridinylmethyl)-Molecular Formula: C17H20N2O2 Molecular Weight: 284.35 g/molPhenylephrine Hydrochloride:Chemical Name: (R)-3-hydroxy-[(methylamino)methyl]benzenemethanol hydrochlorideMolecular Formula: C9H13NO2HClMolecular Weight: 203.67 g/molEach mL of MYDCOMBI ophthalmic spray (sterile) contains: ACTIVES: Phenylephrine Hydrochloride 2.5% (25 mg) equivalent to 20.6 mg of phenylephrine base, Tropicamide 1% (10 mg); INACTIVE: Hydrochloric Acid and/or Sodium Hydroxide may be added to adjust pH (pH 4.8-5.2), Water for Injection; PRESERVATIVE: Benzalkonium Chloride 0.01% (0.1 mg).. Chemical Structure. Chemical Structure.

DOSAGE & ADMINISTRATION SECTION.

2DOSAGE AND ADMINISTRATION. Administer one metered spray to the cornea of each eye to be dilated. Repeat after minutes. (2.1)In pediatric patients younger than year old, administer one metered spray to the cornea of each eye to be dilated, up to maximum of sprays per eye per day (2.1). Administer one metered spray to the cornea of each eye to be dilated. Repeat after minutes. (2.1). In pediatric patients younger than year old, administer one metered spray to the cornea of each eye to be dilated, up to maximum of sprays per eye per day (2.1). 2.1Recommended Dosage. Administer one metered spray to the cornea of each eye to be dilated. Repeat after minutes. Pediatric Patients Younger Than Year OldIn pediatric patients younger than year old, administer one metered spray to the cornea of each eye to be dilated, up to maximum of sprays per eye per day.. 2.2Administration Instructions. The following steps should be followed sequentially:Load the MYDCOMBI dispenser by depressing the FILL BUTTON at the top of the dispenser once.Figure 1: MYDCOMBI Dispenser Front (L) and Back (R) View Hold MydCombi(TM) dispenser with thumb over Mist Button, wrapping other fingers around base.Bring MydCombi(TM) dispenser to patients eye with Mirror facing the eye.-The dispenser should be as close as patients nose.-To prevent blinking, use your other hand to gently pull lower eyelid down or ask patient to pull her/his lid down. Aim Mist Opening toward the center of eye.Confirm Alignment Marks (on the Fill Button and the cartridge side) align with the center of eye.-Ask patient to confirm when their eye is centered on the BLUE Mirror. If patient is having trouble centering their eye on the blue light, ask that they look up, then look at the BLUE Mirror. Firmly press and release Mist Button.-The drug solution should gently wet the eye. Repeat steps to if needed. Administer second metered spray after minutes to each dilated eye.Repeat steps to for the contralateral eye if it is to be dilated.. Load the MYDCOMBI dispenser by depressing the FILL BUTTON at the top of the dispenser once.Figure 1: MYDCOMBI Dispenser Front (L) and Back (R) View Hold MydCombi(TM) dispenser with thumb over Mist Button, wrapping other fingers around base.. Bring MydCombi(TM) dispenser to patients eye with Mirror facing the eye.-The dispenser should be as close as patients nose.-To prevent blinking, use your other hand to gently pull lower eyelid down or ask patient to pull her/his lid down. -The dispenser should be as close as patients nose.. -To prevent blinking, use your other hand to gently pull lower eyelid down or ask patient to pull her/his lid down.. Aim Mist Opening toward the center of eye.. Confirm Alignment Marks (on the Fill Button and the cartridge side) align with the center of eye.-Ask patient to confirm when their eye is centered on the BLUE Mirror. If patient is having trouble centering their eye on the blue light, ask that they look up, then look at the BLUE Mirror. -Ask patient to confirm when their eye is centered on the BLUE Mirror.. Firmly press and release Mist Button.-The drug solution should gently wet the eye. Repeat steps to if needed. -The drug solution should gently wet the eye. Repeat steps to if needed.. Administer second metered spray after minutes to each dilated eye.. Repeat steps to for the contralateral eye if it is to be dilated.. Figure 1.

DOSAGE FORMS & STRENGTHS SECTION.

3DOSAGE FORMS AND STRENGTHS. MYDCOMBI is sterile, clear, colorless, topical ophthalmic spray containing tropicamide 1% (w/w) and phenylephrine hydrochloride 2.5% (w/w). Each metered spray delivers 0.008 mL which contains 0.08 mg tropicamide and 0.2 mg phenylephrine hydrochloride.. Ophthalmic spray containing tropicamide 1% and phenylephrine hydrochloride 2.5%. Each metered spray delivers 0.008 mL which contains 0.08 mg tropicamide and 0.2 mg phenylephrine HCl (3).

DRUG INTERACTIONS SECTION.

7DRUG INTERACTIONS. Atropine-like Drugs: May exaggerate the adrenergic pressor response (7.1)Cholinergic Agonists and Ophthalmic Cholinesterase Inhibitors: May interfere with the antihypertensive action of carbachol, pilocarpine, or ophthalmic cholinesterase inhibitors (7.2)Potent Inhalation Anesthetic Agents: May potentiate cardiovascular depressant effects of (7.3). Atropine-like Drugs: May exaggerate the adrenergic pressor response (7.1). Cholinergic Agonists and Ophthalmic Cholinesterase Inhibitors: May interfere with the antihypertensive action of carbachol, pilocarpine, or ophthalmic cholinesterase inhibitors (7.2). Potent Inhalation Anesthetic Agents: May potentiate cardiovascular depressant effects of (7.3). 7.1Agents That May Exaggerate Pressor Responses. Phenylephrine in MYDCOMBI may enhance the pressor effects of atropine-like drugs and induce tachycardia in some patients.. 7.2Cholinergic Agonists and Ophthalmic Cholinesterase Inhibitors. Tropicamide in MYDCOMBI may interfere with the antihypertensive action of carbachol, pilocarpine, or ophthalmic cholinesterase inhibitors.. 7.3Potent Inhalation Anesthetic Agents. Phenylephrine in MYDCOMBI may potentiate the cardiovascular depressant effects of some inhalation anesthetic agents.

GERIATRIC USE SECTION.

8.5Geriatric Use. No overall differences in safety or effectiveness of MYDCOMBI have been observed between patients 65 years of age and older and younger adult patients.

HOW SUPPLIED SECTION.

14HOW SUPPLIED/STORAGE AND HANDLING. MYDCOMBI is supplied as sterile, clear, colorless solution in 2 mL vial enclosed in dispenser cartridge. Each MYDCOMBI cartridge holds approximately 180 sprays.Do not tamper with or attempt to open the MYDCOMBI cartridge. Such action may damage the dispenser causing an incorrect medication discharge volume; additionally, the dispenser base may not function properly.Only use the MYDCOMBI cartridge with the MYDCOMBI Dispenser base which may be supplied separately. The MYDCOMBI base will not work with any other cartridges.NDC 81046-0111-1. Carton containing one replacement sterile drug cartridgeNDC 81046-0111-2. Box containing one carton with one sterile drug cartridge, and one carton with one base unitNDC 81046-0111-5. Box containing five cartons, each with one replacement sterile drug cartridgeThe MYDCOMBI cartridge must be used prior to the expiration date on the cartridge. Storage: Store at room temperature 15C to 25C (59F to 77F).

INDICATIONS & USAGE SECTION.

1INDICATIONS AND USAGE. MYDCOMBI (tropicamide and phenylephrine hydrochloride ophthalmic spray) 1% 2.5% is indicated to induce mydriasis for diagnostic procedures and in conditions where short term pupil dilation is desired.. MYDCOMBI is combination of tropicamide, an anticholinergic, and phenylephrine hydrochloride, an alpha-1 adrenergic receptor agonist indicated to induce mydriasis for diagnostic procedures and in conditions where short term pupil dilation is desired (1).

INFORMATION FOR PATIENTS SECTION.

15PATIENT COUNSELING INFORMATION. Advise patients that they may experience sensitivity to light and blurred vision while their pupils are dilated. Advise patients not to drive, use machinery, or do any activity that requires clear vision until they are sure they can perform such activities safely.

INSTRUCTIONS FOR USE SECTION.

INSTRUCTIONS FOR USE. MydCombi(TM)(Tropicamide and Phenylephrine HCl Ophthalmic Spray), 1%/2.5%Rx OnlyContentsGetting to know MydCombi(TM)3How the MydCombi(TM) Dispenser Works3Understanding the Mist and Battery Lights4Important Reminders and Cleaning Instructions4Storing the MydCombi(TM) Base and Cartridges5Assembling the MydCombi(TM) Dispenser6Preparing MydCombi(TM) for Use Each Day8Administering MydCombi(TM)9Troubleshooting Tips10Replacing the MydCombi(TM) Cartridge10Symbols Used in Labels on the MydCombi(TM) Cartridge, Base and Packaging11INSTRUCTIONS FOR USEMydCombi(TM) Ophthalmic SprayThis Instructions for Use document has information about the administration of MydCombi(TM) (Tropicamide and Phenylephrine HCI Ophthalmic Spray) 1%/2.5%.MydCombi(TM) is packaged in dispenser that mists drug solution onto the eye. It has parts the cartridge that holds the drug solution, and the base that holds electronics.Getting to know MydCombi(TM)MydCombi(TM) Dispenser PartsMydCombi(TM) AssembledHow the MydCombi(TM) Dispenser WorksThe MydCombi(TM) Cartridge holds the drug solution.The MydCombi(TM) Base supplies power to the dispenser.The Fill Button is pressed to load the drug solution for topical ophthalmic administration. The Mist Opening is where drug solution comes out when the Mist Button is pressed. The Light and Mirror around the Mist Opening and the Eye Alignment Marks on the top and each side of the cartridge help align the eye for drug administration. The Battery Light shows how much electrical charge remains in the Base.The Release Tabs on each side of the cartridge are used to separate the cartridge and base when replacing cartridges.The MydCombi(TM) Base is charged using Micro-USB to USB Cable with Wall Plug or USB port (supplied separately). See MydCombi(TM) Base Charging and Electrical Information .Understanding the Mist and Battery LightsThe Mist Light and the Battery Light show the status of the MydCombi(TM) dispenser. What the Mist and Battery Lights Mean If you see...It means...Mist Light SOLID BLUE Ready to doseMist Light BLINKING BLUE with Battery Light BLINKING RED BLUE Reset the dispenser-See TROUBLESHOOTING TIPS (page 10) for dispenser reset instructions. If lights continue blinking after dispenser reset, reset again. If lights continue to blink after second reset, change the cartridge. Battery Light BLINKING GREEN Battery is chargingBattery Light SOLID GREEN Battery is fully chargedBattery Light BLINKING RED Battery is lowBattery Light SOLID RED Charge dispenser base at onceImportant Reminders and Cleaning InstructionsWash hands prior to using MydCombi(TM).Before each use, the exterior (including the mirror surface) of the dispenser should be cleaned using 70% isopropyl alcohol (IPA) wipe or clean dust-free, cotton cloth dampened with 70% IPA solution.Wipe the exterior for minutes. While wiping, pay close attention to all cracks, crevices, and any other hard to reach areas. Additional wipes may be used as needed. Allow the exterior to air dry. Only manual, non-immersion cleaning as described should be used for the dispenser. Do not autoclave (steam sterilize) or immerse in cleaning fluids. Always disconnect power supply from source before cleaning.If the patient wears soft contact lenses, they should be removed at least 10 minutes before drug administration.If the patient uses artificial tears, they should not be administered within 10 minutes of drug administration.Each MydCombi(TM) cartridge holds approximately 180 sprays.Only use the MydCombi(TM) cartridge with the MydCombi(TM) base. The MydCombi(TM) base will not work with any other type of cartridges.See MydCombi(TM) Base Charging and Electrical Information contained with MydCombi(TM) for complete instruction on charging and applicable electrical information.Storing the MydCombi(TM) Base and CartridgesStore MydCombi(TM) bases and cartridges at room temperature 15C to 25C (59F to 77F). Protect from light and excessive heat.-Do not heat or freeze the MydCombi(TM) base or cartridge.-Do not expose MydCombi(TM) base to fluids.-Do not tamper with or try to open the MydCombi(TM) cartridge or base. Doing so could cause damage and result in personal injury.The MydCombi(TM) base contains lithium-ion battery. Damage to the base can cause fire. Do not puncture base or expose to excessive heat (>= 50C). Li-Ion batteries may pose environmental and safety hazards and should be disposed of in accordance with all applicable Federal and State Laws. Check with all governing travel bodies for current requirements before air travel.Assembling the MydCombi(TM) DispenserComplete these steps to assemble the MydCombi(TM) base and cartridge.Note: If packaging is opened or damaged, do not use the contents. Instead, open new base or cartridge, and contact your distributer for replacement.1.Assemblea.Remove base and/or cartridge from packaging.b.Align base and cartridge, then press together until they click.-Take care to avoid pressing Fill Button when assembling.2.ChargeCharge MydCombi(TM) base before first use (see MydCombi Base Charging and Electrical Information contained with MydCombi(TM) base packaging). Charging may be performed either before or after assembly.a.Push micro-USB cable into Charging Port.b.Connect opposite end of USB cable to wall outlet plug or USB port.-Battery light BLINKS GREEN while charging.c.Charge until battery light turns SOLID GREEN, then disconnect cable from Charging Port.Note: Excessive charging may damage battery or decrease battery life. Charging weekly, or when the Battery Light begins blinking red (signaling low battery) is recommended. 3.Primea.Hold MydCombi(TM) dispenser upright.b.Firmly press Fill Button down until it stops, and Mist Light turns Blue.c.Slowly release Fill Button, while counting to 3.-If Fill Button does not return to position, press again until it is all the way down.-If Fill Button still does not return to position, get new cartridge, and re-assemble (Steps - [page 6]). d.Point Mist Opening away from face.e.Firmly press, then release Mist Button.f.Repeat Steps - until mist emerges from opening.-If mist does not come out after repeating these steps times, get new cartridge and re-assemble (Steps - [page 6]). 4.MydCombi(TM) is now ready to use.Preparing MydCombi(TM) for Use Each DayImportant: test mist must be performed each day before dosing is commenced. 1.Load drug solutiona.Hold MydCombi(TM) dispenser upright.b.Firmly press Fill Button down until it stops, and Mist Light turns Blue.c.Slowly release Fill Button, while counting to 3.-If Fill Button does not return to position, press again until it is all the way down.-If Fill Button still does not return to position, get new cartridge, and re-assemble (Steps - [page 6]). 2.Do test mista.Holding MydCombi(TM) dispenser upright, point Mist Opening away from face.b.Firmly press and release Mist Button.3.MydCombi(TM) is ready to use.Administering MydCombi(TM)Important: Keep MydCombi(TM) dispenser upright during use to maintain dose volume.1.Load drug solutiona.Hold MydCombi(TM) dispenser upright and firmly press Fill Button down until it stops, and Mist Light turns Blue.b.Slowly release Fill Button, while counting to 3.2.Align MydCombi(TM) with patients eyea.Hold MydCombi(TM) dispenser with thumb over Mist Button, wrapping other fingers around base. b.Bring MydCombi(TM) dispenser to patients eye with Mirror facing the eye.-The dispenser should be as close as patients nose.-To prevent blinking, use your other hand to gently pull lower eyelid down or ask patient to pull her/his lid down. c.Aim Mist Opening toward the center of eye.d.Confirm Alignment Marks (on the Fill Button and the cartridge side) align with the center of eye.-Ask patient to confirm when their eye is centered on the BLUE Mirror.If patient is having trouble centering their eye on the blue light, ask that they look up, then look at the BLUE Mirror.3.Press Mist Buttona.Firmly press and release Mist Button.-The drug solution should gently wet the eye. Repeat Steps 1-3 if needed.Troubleshooting TipsIf no mist comes out when Mist Button is pressed, confirm Fill Button has been pressed down completely, and has returned to the up position.If solution is not administered within minute after loading, it will be automatically discharged the MIST Light will blink blue while the Battery Light blinks red and blue. The MydCombi(TM) dispenser must be reset using the steps below. To reset dispenser: -Press and release Mist Button.-Press and release Fill Button.-Press and release Mist Button again.-Reload solution (Step [page 9]). To report suspected adverse reactions please contact Eyenovia, Inc at 1-833-393-6684 (Option 1) or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch.Replacing the MydCombi(TM) Cartridge1.Remove cartridgea.Hold MydCombi(TM) base in one hand. With other hand, press and squeeze Release Tabs on each side of cartridge.b.Pull cartridge and base apart.c.Place used cartridge in original tray and box for disposal or recycling.Symbols Used in Labels on the MydCombi(TM) Cartridge, Base and PackagingSYMBOLDEFINITIONSYMBOLDEFINITIONCAUTION, CONSULT ACCOMPANYING DOCUMENTSUSE BY (YYYY-MM: YEAR-MONTH)SEE INSTRUCTIONS FOR USESTERILIZED USING ETHYLENE OXIDECATALOG NUMBERNON-STERILEBATCH CODEDO NOT RESTERILIZEQUANTITYLITHIUM-ION BATTERY TO BE APPROPRIATELY RECYCLEDDATE OF MANUFACTURE (YYYY-MM YEAR-MONTH)KEEP DRYMANUFACTURERGHS LITHIUM-ION DISPOSALDO NOT USE IF THE PACKAGING HAS BEEN OPENED OR DAMAGEDELECTRONIC EQUIPMENT. DO NOT THROW IN TRASH.WARNING: ELECTRICITYBY PRESCRIPTION ONLYPROTECTED AGAINST VERTICALLY FALLING WATER DROPS UP TO 15-DEGREE ANGLETYPE BF PART COMPLYING WITH IEC 60601-1Manufactured By:Eyenovia295 Madison Ave., Suite 2400New York, NY 10017(C) 2022 Eyenovia, Inc. All rights reserved.. The MydCombi(TM) Cartridge holds the drug solution.. The MydCombi(TM) Base supplies power to the dispenser.. The Fill Button is pressed to load the drug solution for topical ophthalmic administration. The Mist Opening is where drug solution comes out when the Mist Button is pressed. The Light and Mirror around the Mist Opening and the Eye Alignment Marks on the top and each side of the cartridge help align the eye for drug administration. The Battery Light shows how much electrical charge remains in the Base.. The Release Tabs on each side of the cartridge are used to separate the cartridge and base when replacing cartridges.. The MydCombi(TM) Base is charged using Micro-USB to USB Cable with Wall Plug or USB port (supplied separately). See MydCombi(TM) Base Charging and Electrical Information .. -See TROUBLESHOOTING TIPS (page 10) for dispenser reset instructions. Wash hands prior to using MydCombi(TM).. Before each use, the exterior (including the mirror surface) of the dispenser should be cleaned using 70% isopropyl alcohol (IPA) wipe or clean dust-free, cotton cloth dampened with 70% IPA solution.. Wipe the exterior for minutes. While wiping, pay close attention to all cracks, crevices, and any other hard to reach areas. Additional wipes may be used as needed. Allow the exterior to air dry. Only manual, non-immersion cleaning as described should be used for the dispenser. Do not autoclave (steam sterilize) or immerse in cleaning fluids. Always disconnect power supply from source before cleaning.. If the patient wears soft contact lenses, they should be removed at least 10 minutes before drug administration.. If the patient uses artificial tears, they should not be administered within 10 minutes of drug administration.. Each MydCombi(TM) cartridge holds approximately 180 sprays.. Only use the MydCombi(TM) cartridge with the MydCombi(TM) base. The MydCombi(TM) base will not work with any other type of cartridges.. See MydCombi(TM) Base Charging and Electrical Information contained with MydCombi(TM) for complete instruction on charging and applicable electrical information.. -Do not heat or freeze the MydCombi(TM) base or cartridge.. -Do not expose MydCombi(TM) base to fluids.. -Do not tamper with or try to open the MydCombi(TM) cartridge or base. Doing so could cause damage and result in personal injury.. 1.Assemblea.Remove base and/or cartridge from packaging.b.Align base and cartridge, then press together until they click.-Take care to avoid pressing Fill Button when assembling.. a.Remove base and/or cartridge from packaging.. b.Align base and cartridge, then press together until they click.-Take care to avoid pressing Fill Button when assembling.. -Take care to avoid pressing Fill Button when assembling.. 2.ChargeCharge MydCombi(TM) base before first use (see MydCombi Base Charging and Electrical Information contained with MydCombi(TM) base packaging). Charging may be performed either before or after assembly.a.Push micro-USB cable into Charging Port.b.Connect opposite end of USB cable to wall outlet plug or USB port.-Battery light BLINKS GREEN while charging.c.Charge until battery light turns SOLID GREEN, then disconnect cable from Charging Port.Note: Excessive charging may damage battery or decrease battery life. Charging weekly, or when the Battery Light begins blinking red (signaling low battery) is recommended. a.Push micro-USB cable into Charging Port.. b.Connect opposite end of USB cable to wall outlet plug or USB port.-Battery light BLINKS GREEN while charging.. -Battery light BLINKS GREEN while charging.. c.Charge until battery light turns SOLID GREEN, then disconnect cable from Charging Port.. 3.Primea.Hold MydCombi(TM) dispenser upright.b.Firmly press Fill Button down until it stops, and Mist Light turns Blue.c.Slowly release Fill Button, while counting to 3.-If Fill Button does not return to position, press again until it is all the way down.-If Fill Button still does not return to position, get new cartridge, and re-assemble (Steps - [page 6]). a.Hold MydCombi(TM) dispenser upright.. b.Firmly press Fill Button down until it stops, and Mist Light turns Blue.. c.Slowly release Fill Button, while counting to 3.-If Fill Button does not return to position, press again until it is all the way down.-If Fill Button still does not return to position, get new cartridge, and re-assemble (Steps - [page 6]). -If Fill Button does not return to position, press again until it is all the way down.. -If Fill Button still does not return to position, get new cartridge, and re-assemble (Steps - [page 6]). d.Point Mist Opening away from face.e.Firmly press, then release Mist Button.f.Repeat Steps - until mist emerges from opening.-If mist does not come out after repeating these steps times, get new cartridge and re-assemble (Steps - [page 6]). d.Point Mist Opening away from face.. e.Firmly press, then release Mist Button.. f.Repeat Steps - until mist emerges from opening.-If mist does not come out after repeating these steps times, get new cartridge and re-assemble (Steps - [page 6]). -If mist does not come out after repeating these steps times, get new cartridge and re-assemble (Steps - [page 6]). 4.MydCombi(TM) is now ready to use.. 1.Load drug solutiona.Hold MydCombi(TM) dispenser upright.b.Firmly press Fill Button down until it stops, and Mist Light turns Blue.c.Slowly release Fill Button, while counting to 3.-If Fill Button does not return to position, press again until it is all the way down.-If Fill Button still does not return to position, get new cartridge, and re-assemble (Steps - [page 6]). a.Hold MydCombi(TM) dispenser upright.. b.Firmly press Fill Button down until it stops, and Mist Light turns Blue.. c.Slowly release Fill Button, while counting to 3.-If Fill Button does not return to position, press again until it is all the way down.-If Fill Button still does not return to position, get new cartridge, and re-assemble (Steps - [page 6]). -If Fill Button does not return to position, press again until it is all the way down.. -If Fill Button still does not return to position, get new cartridge, and re-assemble (Steps - [page 6]). 2.Do test mista.Holding MydCombi(TM) dispenser upright, point Mist Opening away from face.b.Firmly press and release Mist Button.. a.Holding MydCombi(TM) dispenser upright, point Mist Opening away from face.. b.Firmly press and release Mist Button.. 3.MydCombi(TM) is ready to use.. 1.Load drug solutiona.Hold MydCombi(TM) dispenser upright and firmly press Fill Button down until it stops, and Mist Light turns Blue.b.Slowly release Fill Button, while counting to 3.. a.Hold MydCombi(TM) dispenser upright and firmly press Fill Button down until it stops, and Mist Light turns Blue.. b.Slowly release Fill Button, while counting to 3.. 2.Align MydCombi(TM) with patients eyea.Hold MydCombi(TM) dispenser with thumb over Mist Button, wrapping other fingers around base. b.Bring MydCombi(TM) dispenser to patients eye with Mirror facing the eye.-The dispenser should be as close as patients nose.-To prevent blinking, use your other hand to gently pull lower eyelid down or ask patient to pull her/his lid down. c.Aim Mist Opening toward the center of eye.d.Confirm Alignment Marks (on the Fill Button and the cartridge side) align with the center of eye.-Ask patient to confirm when their eye is centered on the BLUE Mirror.If patient is having trouble centering their eye on the blue light, ask that they look up, then look at the BLUE Mirror.. a.Hold MydCombi(TM) dispenser with thumb over Mist Button, wrapping other fingers around base. b.Bring MydCombi(TM) dispenser to patients eye with Mirror facing the eye.-The dispenser should be as close as patients nose.-To prevent blinking, use your other hand to gently pull lower eyelid down or ask patient to pull her/his lid down. -The dispenser should be as close as patients nose.. -To prevent blinking, use your other hand to gently pull lower eyelid down or ask patient to pull her/his lid down.. c.Aim Mist Opening toward the center of eye.. d.Confirm Alignment Marks (on the Fill Button and the cartridge side) align with the center of eye.-Ask patient to confirm when their eye is centered on the BLUE Mirror.. -Ask patient to confirm when their eye is centered on the BLUE Mirror.. 3.Press Mist Buttona.Firmly press and release Mist Button.-The drug solution should gently wet the eye. Repeat Steps 1-3 if needed.. a.Firmly press and release Mist Button.-The drug solution should gently wet the eye. Repeat Steps 1-3 if needed.. -The drug solution should gently wet the eye. Repeat Steps 1-3 if needed.. If no mist comes out when Mist Button is pressed, confirm Fill Button has been pressed down completely, and has returned to the up position.. If solution is not administered within minute after loading, it will be automatically discharged the MIST Light will blink blue while the Battery Light blinks red and blue. The MydCombi(TM) dispenser must be reset using the steps below. To reset dispenser: -Press and release Mist Button.-Press and release Fill Button.-Press and release Mist Button again.-Reload solution (Step [page 9]). -Press and release Mist Button.. -Press and release Fill Button.. -Press and release Mist Button again.. -Reload solution (Step [page 9]).. 1.Remove cartridgea.Hold MydCombi(TM) base in one hand. With other hand, press and squeeze Release Tabs on each side of cartridge.b.Pull cartridge and base apart.c.Place used cartridge in original tray and box for disposal or recycling.. a.Hold MydCombi(TM) base in one hand. With other hand, press and squeeze Release Tabs on each side of cartridge.. b.Pull cartridge and base apart.. c.Place used cartridge in original tray and box for disposal or recycling.. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure. Figure.

LACTATION SECTION.

8.2Lactation. Risk SummaryThere are no data on the presence of tropicamide or phenylephrine in human milk from the administration of MYDCOMBI, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for MYDCOMBI and any potential adverse effects on the breastfed child from MYDCOMBI.

MECHANISM OF ACTION SECTION.

12.1Mechanism of Action. Tropicamide, the anticholinergic component of MYDCOMBI, blocks the responses of the sphincter muscle of the iris, dilating the pupil (mydriasis). Phenylephrine hydrochloride, the alpha-1 adrenergic agonist component of MYDCOMBI, acts as mydriatic agent by contracting the dilator muscle of the iris.

OVERDOSAGE SECTION.

10OVERDOSAGE. Overdosage of MYDCOMBI may cause rapid rise in blood pressure. It may also cause headache, anxiety, nausea and vomiting, and ventricular arrhythmias. Prompt injection of rapidly acting alpha- adrenergic blocking agent such as phentolamine has been recommended.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL MYDCOMBI Base Unit Label. MydCombi(TM) BaseNon-SterileREF FG-16427 LOT F-YYYY-MM-DDLi-ion15C59F25C77FIPX2Eyenovia, Inc.295 Madison Ave, Ste 2400New York, NY 10017(01) 008600099909700(10) F-123465(17) 250405Rx ONLYLS-17076-E. Principal Display Panel MYDCOMBI Base Unit Label.

PEDIATRIC USE SECTION.

8.4Pediatric Use. Tropicamide in MYDCOMBI may rarely cause CNS disturbances which may be dangerous in pediatric patients. Psychotic reactions, behavioral disturbances, and vasomotor or cardiorespiratory collapse in children have been reported with the use of anticholinergic drugs [see Warnings and Precautions (5.3)].

PHARMACODYNAMICS SECTION.

12.2Pharmacodynamics. MYDCOMBI acts in 15 to 30 minutes with maximal mydriasis occurring in 20 to 90 minutes. Darker irides tend to dilate slower than lightly pigmented irides and to achieve maximal effect may require more doses than lighter irides.Mydriasis will reverse spontaneously with time, with recovery after to hours. Complete recovery from mydriasis in some individuals may require 24 hours.

PREGNANCY SECTION.

8.1Pregnancy. Risk SummaryThere are no available data on MYDCOMBI use in pregnant women or animals to inform any drug-associated risks. It is also not known whether tropicamide or phenylephrine can cause fetal harm when administered to pregnant woman or can affect reproduction capacity. MYDCOMBI should be given to pregnant woman only if clearly needed.

SPL UNCLASSIFIED SECTION.

2.1Recommended Dosage. Administer one metered spray to the cornea of each eye to be dilated. Repeat after minutes. Pediatric Patients Younger Than Year OldIn pediatric patients younger than year old, administer one metered spray to the cornea of each eye to be dilated, up to maximum of sprays per eye per day.

STORAGE AND HANDLING SECTION.

Storage: Store at room temperature 15C to 25C (59F to 77F).

USE IN SPECIFIC POPULATIONS SECTION.

8USE IN SPECIFIC POPULATIONS. Pediatric Use: May rarely cause central nervous system disturbances which may be dangerous in pediatric patients (5.3, 8.4). 8.1Pregnancy. Risk SummaryThere are no available data on MYDCOMBI use in pregnant women or animals to inform any drug-associated risks. It is also not known whether tropicamide or phenylephrine can cause fetal harm when administered to pregnant woman or can affect reproduction capacity. MYDCOMBI should be given to pregnant woman only if clearly needed.. 8.2Lactation. Risk SummaryThere are no data on the presence of tropicamide or phenylephrine in human milk from the administration of MYDCOMBI, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for MYDCOMBI and any potential adverse effects on the breastfed child from MYDCOMBI.. 8.4Pediatric Use. Tropicamide in MYDCOMBI may rarely cause CNS disturbances which may be dangerous in pediatric patients. Psychotic reactions, behavioral disturbances, and vasomotor or cardiorespiratory collapse in children have been reported with the use of anticholinergic drugs [see Warnings and Precautions (5.3)]. 8.5Geriatric Use. No overall differences in safety or effectiveness of MYDCOMBI have been observed between patients 65 years of age and older and younger adult patients.

WARNINGS AND PRECAUTIONS SECTION.

5WARNINGS AND PRECAUTIONS. Not for Injection: Topical ophthalmic use (5.1)Significant Elevations in Blood Pressure: Caution in pediatric patients less than years of age, and in patients with cardiovascular disease or hyperthyroidism. In patients at high risk, monitor blood pressure post treatment (5.2)Central Nervous System Disturbances: Caution in pediatric patients where rare incidences of central nervous system disturbances have been reported (5.3)Intraocular Pressure: May produce transient elevation (5.4)Rebound Miosis: Reported day after administration (5.5). Not for Injection: Topical ophthalmic use (5.1). Significant Elevations in Blood Pressure: Caution in pediatric patients less than years of age, and in patients with cardiovascular disease or hyperthyroidism. In patients at high risk, monitor blood pressure post treatment (5.2). Central Nervous System Disturbances: Caution in pediatric patients where rare incidences of central nervous system disturbances have been reported (5.3). Intraocular Pressure: May produce transient elevation (5.4). Rebound Miosis: Reported day after administration (5.5). 5.1Topical Ophthalmic Use MYDCOMBI is not indicated for injection.. 5.2Blood Pressure Elevation. Caution should be exercised with the use of MYDCOMBI in pediatric patients less than years of age and patients with hyperthyroidism, or cardiovascular disease. The post-treatment blood pressure of patients with cardiac and endocrine diseases and any patients who develop symptoms should be carefully monitored.. 5.3Central Nervous System Disturbances. Tropicamide in MYDCOMBI may cause CNS disturbances which may be dangerous in pediatric patients. The possibility of psychotic reactions and behavioral disturbances due to hypersensitivity to anticholinergic drugs should be considered.. 5.4Intraocular Pressure. Mydriatics may produce transient elevation of intraocular pressure.. 5.5Rebound Miosis. Rebound miosis has been reported one day after receiving phenylephrine hydrochloride ophthalmic solution, and re-administration of the drug produced lesser mydriatic effect.