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  • CLASSES

    Hypotrichosis Agent
    Prostaglandins, Ophthalmic

    DEA CLASS

    Rx

    DESCRIPTION

    Synthetic analog of prostaglandin; available as an ophthalmic solution and intracameral implant
    Used to lower IOP in patients with open-angle glaucoma or ocular hypertension; also approved for hypotrichosis
    Associated with increased pigmentation of eyelashes, iris, and periorbital tissue; changes in iridal pigmentation may be permanent

    COMMON BRAND NAMES

    DURYSTA, Latisse, Lumigan

    HOW SUPPLIED

    Bimatoprost/Latisse/Lumigan Ophthalmic Sol: 0.01%, 0.03%
    DURYSTA Intracameral Imp: 10mcg

    DOSAGE & INDICATIONS

    For the reduction of elevated or increased intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.
    Ophthalmic dosage (Lumigan ophthalmic solution)
    Adults

    Instill 1 drop to the affected eye(s) once daily in the evening. More frequent administration may decrease the IOP-lowering effect.

    Adolescents 16 years and older

    Instill 1 drop to the affected eye(s) once daily in the evening. More frequent administration may decrease the IOP-lowering effect.

    Intracameral dosage (Durysta intracameral implant)
    Adults

    Insert a single 10 mcg biodegradable implant via intracameral injection. Perform the injection under magnification and standard aseptic conditions, with the patient's head in a stabilized position. DO NOT dilate the eye prior to the procedure. DO NOT retreat an eye that has already received an implant.

    For treatment of hypotrichosis of the eyelashes.
    Ophthalmic dosage (Latisse 0.03% ophthalmic solution)
    Adults

    Apply 1 drop to each eye at night using the supplied applicator; apply evenly along the skin of the upper eyelid margin at the base of the eyelashes. Do not apply to lower lashes. Additional applications will not further increase the growth of eyelashes. Upon discontinuation, eyelash growth is expected to return to its pre-treatment level.

    Children >= 5 years and Adolescents

    Apply 1 drop to each eye at night using the supplied applicator; apply evenly along the skin of the upper eyelid margin at the base of the eyelashes. Do not apply to lower lashes. Bimatoprost has been studied in children and adolescents 5—17 years who were post-chemotherapy or had alopecia areata and in adolescents 15—17 years with hypotrichosis not associated with a medical condition. Upon discontinuation, eyelash growth is expected to return to its pre-treatment level.

    MAXIMUM DOSAGE

    Adults

    1 drop/day of the ophthalmic solution instilled in each affected eye or applied to each upper eyelid; a single 10 mcg implant inserted via intracameral injection.

    Geriatric

    1 drop/day of the ophthalmic solution instilled in each affected eye or applied to each upper eyelid; a single 10 mcg implant inserted via intracameral injection.

    Adolescents

    1 drop/day of the ophthalmic solution applied to each upper eyelid; safety and efficacy of the intracameral implant have not been established.

    Children

    5 years and older: 1 drop/day of the ophthalmic solution applied to each upper eyelid; safety and efficacy of the intracameral implant have not been established.
    younger than 5 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustment in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustment in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Ophthalmic Administration

    Instruct the patient on the proper use of bimatoprost.
    Wash hands before and after use.
    Contact lenses should be removed prior to ocular application and may be reinserted 15 minutes following drug administration. Lumigan contains the preservative benzalkonium chloride, which may be absorbed by soft contact lenses.
    Lumigan administration:
    Lumigan (bimatoprost ophthalmic solution) is for ophthalmic use only.
    Tilt the head back slightly and pull the lower eyelid down with the index finger to form a pouch. Squeeze the prescribed number of drops into the pouch and gently close the eyes for 1 to 2 minutes. Do not blink.
    To avoid contamination, do not touch the tip of the dropper to the eye, fingertips, or other surfaces.
    The solution may be used concomitantly with other topical ophthalmic drug products to lower IOP. If more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes apart.[41772] [62182]
    Latisse administration:
    Prior to use, ensure the patient's face is clean and makeup removed.
    The disposable sterile applicator is the only applicator that should be used. Each applicator should be used for 1 eye only; dispose of the applicator after each use.
    After applying 1 drop of solution to the applicator, apply evenly along the skin of the upper eyelid margin at the base of the eyelashes. The upper lid margin in the area of eyelash growth should feel lightly moist without runoff. Blot excess solution runoff outside the upper eyelid margin with a tissue or other absorbent cloth.
    Do not apply to the lower eyelash line.[34734]

    Other Administration Route(s)

    Intracameral Administration
    DO NOT dilate the eye prior to the procedure and DO NOT readminister to an eye that has already been treated with an insert.
    Perform the injection using standard aseptic conditions for intracameral injection and under magnification that allow clear visualization of the anterior changer structures.
    Ensure the patient's head is in a stabilized position.
    Remove the foil pouch from the carton and inspect it for damage. Open the pouch over a sterile field and gently drop the applicator on a sterile tray. Once the pouch is opened, the applicator should be used promptly.
    Inspect the applicator. Ensure the actuator button has not been depressed, and the safety tab is in place. Remove the plastic safety cap taking care to avoid contact with the needle tip. Inspect the tip for damage under magnification; the implant retention plug may be visible in the bevel and SHOULD NOT be removed.
    Remove the safety tab by pulling it out perpendicular to the long axis of the applicator. Do not twist or bend the tab.
    Stabilize the eye as the needle is advanced through the cornea. Enter the anterior chamber with the needle bevel visible through clear cornea. Enter parallel to the iris plane, adjacent to the limbus through clear cornea in the superotemporal quadrant.
    Insert the needle approximately 2 bevel lengths with the bevel completely within the anterior chamber; avoid positioning the needle bevel directly over the pupil. Ensure the needle is not bent before depressing the actuator button.
    Depress the back half of the actuator button firmly until an audible or palpable click is noted.
    After releasing the implant, remove the needle via the same track in which it was inserted and tamponade the opening. The implant should not be left in the corneal injection track.
    Check the injection site for leaks; make sure that it is self-sealing and the anterior chamber is formed.
    Dispose of the applicator in a sharps container without recapping the needle.
    Instruct the patient to remain upright for at least 1 hour after the procedure so the implant can settle.
    Instruct the patients to immediately contact the physician if the eye becomes progressively red, sensitive to light, painful, or if the patient develops a change in vision.[65083]

    STORAGE

    DURYSTA:
    - Refrigerate (between 36 and 46 degrees F)
    Latisse:
    - Store between 36 to 77 degrees F
    Lumigan:
    - Store between 36 to 77 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Bimatoprost is contraindicated in patients with hypersensitivity to bimatoprost.[34734] [41772] [62182] [65083]

    Closed-angle glaucoma

    Avoid the use of bimatoprost in patients with closed-angle glaucoma, or inflammatory or neovascular glaucoma. Further, because the bimatoprost intracameral implant is intended to settle within the inferior angle, caution is advised when using the implant in patients with narrow iridocorneal angles (Shaffer grade less than 3) or anatomical obstruction (e.g., scarring) that may prohibit settling in the inferior angle.

    Aphakia, corneal abrasion, corneal transplant, iritis, keratitis, ocular infection, ocular surgery, ocular trauma, uveitis

    Bimatoprost intracameral implants are contraindicated for use in patients with an active or suspected periocular or ocular infection, corneal endothelial cell dystrophy (e.g., Fuchs' Dystrophy), prior corneal transplant (corneal transplantation) or endothelial cell transplants [e.g., Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK)], and in patients with an absent or ruptured posterior lens capsule (NOTE: laser posterior capsulotomy in pseudophakic patients is not a contraindication if the intraocular lens fully covers the opening in the posterior capsule). The presence of the implant has been associated with corneal adverse reactions and increased risk of corneal endothelial cell loss; therefore, use of the drug should be limited to a single implant per eye without retreatment. Additionally, the implant should be administered with caution to patients with limited corneal endothelial cell reserve. All bimatoprost formulations should be used with caution in patients with active intraocular inflammation (e.g., iritis, uveitis). Prostaglandin analogs have been reported to cause intraocular inflammation, and use in patients with active intraocular inflammation may exacerbate the condition. Bacterial keratitis has been associated with the use of multiple-dose ophthalmic containers, such as bimatoprost ophthalmic solution. Inadvertent contamination of the bimatoprost containers may increase the risk of infection in ocular surgery patients, or in patients who develop an ocular infection or ocular trauma, including corneal abrasion. Proper aseptic techniques must also be employed when inserting the bimatoprost implant, as intraocular injections have been associated with endophthalmitis. If there is any damage to the ocular epithelial surface, bimatoprost should be used with caution. Bimatoprost should be used with caution in patients with aphakia, pseudophakic patients with a torn posterior lens capsule, and patients with known risk factors for macular edema. Macular edema, including cystoid macular edema, has been reported during treatment with bimatoprost.[41772] [65083]

    Contact lenses

    Contact lenses should be removed prior to administration of bimatoprost ophthalmic solution and may be reinserted after 15 minutes. Bimatoprost ophthalmic solution contains the preservative benzalkonium chloride, which may be absorbed by and cause discoloration of soft contact lenses.[34734] [41772][62182]

    Sunlight (UV) exposure

    Bimatoprost may gradually change eye color, increasing the amount of brown pigment in the iris; this change is likely to be permanent. Inform patients of the possibility of iridal discoloration. While treatment may be continued, patients who develop noticeably increased iris pigmentation should be examined regularly. Some patients may also develop photophobia and may be more sensitive to sunlight (UV) exposure.

    Children, infants, neonates

    Safety and efficacy of the bimatoprost intracameral insert in pediatric patients have not been established.[65083] The use of the ophthalmic solution for the reduction of intraocular pressure in neonates, infants, children, and adolescents younger than 16 years is not recommended because of potential safety concerns related to increased pigmentation after long-term chronic use.[41772] Safety and efficacy of bimatoprost for hypotrichosis has not been established for neonates, infants, and children younger than 5 years of age. The use of bimatoprost for hypotrichosis has been studied in children and adolescents 5 to 17 years who were post-chemotherapy or had alopecia areata and in adolescents 15 to 17 years with hypotrichosis not associated with a medical condition.[34734]

    Pregnancy

    There are no adequate and well-controlled studies regarding the use of bimatoprost in pregnant women. Data from postmarketing use of the ophthalmic solution has not identified an increased risk of major birth defects or miscarriages. Further, oral administration of bimatoprost to pregnant rats and mice throughout organogenesis did not produce adverse maternal or fetal effects at clinically relevant exposures. Administer bimatoprost during pregnancy only if the potential benefit justifies the potential risk to the fetus.

    Breast-feeding

    According to the manufacturer, caution should be exercised when bimatoprost is administered to a breast-feeding woman. There are no data regarding the presence of bimatoprost in human milk, the drug's effects on milk production, or the effects on a breast-fed infant. After administering the ophthalmic solution, apply pressure over the tear duct by the corner of the eye for 1 minute to minimize the amount of drug that reaches the systemic circulation and breast milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    ADVERSE REACTIONS

    Severe

    corneal erosion / Delayed / 0-10.0
    keratitis / Delayed / 0-10.0
    ocular hypertension / Delayed / 0-10.0
    visual impairment / Early / 0-10.0
    corneal degeneration / Delayed / 0-1.0
    corneal opacification / Delayed / 0-1.0
    uveitis / Delayed / 0-1.0
    ocular hemorrhage / Delayed / Incidence not known
    macular edema / Delayed / Incidence not known

    Moderate

    conjunctival hyperemia / Early / 0-27.0
    blepharitis / Early / 0-10.0
    photophobia / Early / 0-10.0
    cataracts / Delayed / 0-10.0
    blurred vision / Early / 0-10.0
    iritis / Delayed / 0-10.0
    corneal edema / Early / 1.0-5.0
    erythema / Early / 1.0-4.0
    conjunctivitis / Delayed / 1.0-3.0
    ocular inflammation / Early / 0-1.0
    hyphema / Delayed / 0-1.0
    hypertension / Early / Incidence not known
    dyspnea / Early / Incidence not known

    Mild

    ocular pruritus / Rapid / 0-15.0
    foreign body sensation / Rapid / 0-10.0
    ocular pain / Early / 0-10.0
    ocular irritation / Rapid / 0-10.0
    xerophthalmia / Early / 0-10.0
    skin hyperpigmentation / Delayed / 1.0-10.0
    iridal discoloration / Delayed / 1.0-5.0
    asthenia / Delayed / 1.0-5.0
    headache / Early / 1.0-5.0
    hirsutism / Delayed / 1.0-5.0
    lacrimation / Early / 1.0-4.0
    ocular discharge / Delayed / 1.0-3.0
    hypertrichosis / Delayed / 1.0
    ptosis / Delayed / Incidence not known
    skin discoloration / Delayed / Incidence not known
    nausea / Early / Incidence not known
    dizziness / Early / Incidence not known
    infection / Delayed / Incidence not known
    maculopapular rash / Early / Incidence not known

    DRUG INTERACTIONS

    There are no drug interactions associated with Bimatoprost products.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate and well-controlled studies regarding the use of bimatoprost in pregnant women. Data from postmarketing use of the ophthalmic solution has not identified an increased risk of major birth defects or miscarriages. Further, oral administration of bimatoprost to pregnant rats and mice throughout organogenesis did not produce adverse maternal or fetal effects at clinically relevant exposures. Administer bimatoprost during pregnancy only if the potential benefit justifies the potential risk to the fetus.

    According to the manufacturer, caution should be exercised when bimatoprost is administered to a breast-feeding woman. There are no data regarding the presence of bimatoprost in human milk, the drug's effects on milk production, or the effects on a breast-fed infant. After administering the ophthalmic solution, apply pressure over the tear duct by the corner of the eye for 1 minute to minimize the amount of drug that reaches the systemic circulation and breast milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    •reduction of intraocular pressure (IOP): Bimatoprost selectively mimics endogenous prostamides to produce ocular hypotension. IOP is thought to be reduced by increased aqueous humor outflow through both trabecular network and uveoscleral routes. In vitro biological assays suggest that bimatoprost and related prostamides may also activate novel receptors, which have not yet been identified.
    •promotion of eyelash growth: The mechanism for promotion of eyelash growth is not known; however, an increase in the percent of hairs and an increase in the duration of the hair growth (anagen) phase is postulated.

    PHARMACOKINETICS

    Bimatoprost ophthalmic solution is applied topically to the eye and the intracameral implant is inserted via intraocular injection. Once in the systemic circulation, the drug moderately distributes into body tissues with a steady-state volume of distribution of 0.67 L/kg. In the blood, bimatoprost stays mainly in the plasma with approximately 12% of the drug remaining unbound in human plasma. Bimatoprost is metabolized via oxidation, n-deethylation, and glucuronidation to form a variety of metabolites. The elimination half-life is approximately 45 minutes with a total blood clearance of 1.5 L/hr/kg. Up to 67% of the administered dose is excreted in the urine while 25% of the dose was recovered in the feces.
    Affected cytochrome P450 isoenzymes: none

    Other Route(s)

    Ophthalmic Route
    The pharmacokinetic parameters of bimatoprost were evaluated in 15 healthy subjects who received 1 drop of the 0.03% ophthalmic solution once daily into both eyes for 2 weeks. Peak blood concentrations (Cmax) were achieved within 10 minutes after each dose and, in most subjects, dropped below the lower limit of detection (0.025 ng/mL) within 1.5 hours. Mean Cmax and exposure values were similar on days 7 and 14 at approximately 0.08 ng/mL and 0.09 ng x hr/mL, respectively, indicating that steady-state was reached during the first week of ocular dosing. There was no significant systemic drug accumulation with repeated dosing.
     
    Intracameral Route
    Following the insertion of a single 10 mcg implant, bimatoprost concentrations were below the lower limit of quantitation (0.001 ng/mL) in approximately 92% of drug recipients. The maximum observed drug concentration in any subject was 0.00224 ng/mL. Similarily, bimatoprost acid concentrations were also below the lower limit of quantitation in almost all (approximately 99%) drug recipients.