Bimatoprost is a synthetic structural analog of prostaglandin F2-alpha (prostamide F2-alpha) indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. The drug lowers IOP by increasing the outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes. Bimatoprost is also approved for the treatment of hypotrichosis of the eyelashes. In patients with hypotrichosis, bimatoprost increased eyelash prominence, length, fullness or thickness, and darkness after 8, 12, and 16 weeks of use. The drug is commercially available as an ophthalmic solution (0.1% and 0.3%) and as a 10 mcg intracameral implant; the intracameral implant must be inserted by a health care professional under standard aseptic conditions. As with latanoprost and travoprost, bimatoprost has been associated with changes to pigmented tissues including increased pigmentation of eyelashes, the iris, and periorbital tissue. Changes in iridal pigmentation may be permanent.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific 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.
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.
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.
Bimatoprost may gradually change eyelashes and vellus hair. These changes include increased length, thickness, and number of eyelashes (hypertrichosis). While this effect is the desired outcome for some formulations of bimatoprost, these changes can also occur with use of the product for elevated intraocular pressure (IOP). Reported occurrence varies based on the product and is reported between 1% and 4% with one product and more than 15% with another product. Eyelash changes are usually reversible upon discontinuation of treatment. Hair growth may also occur in areas where bimatoprost comes in repeated contact with the surface of the skin. In postmarketing reports, madarosis (temporary loss of a few eyelashes to loss of sections of eyelashes), trichorrhexis (temporary eyelash breakage), and trichiasis were noted.
Ocular adverse effects frequently associated with the use of bimatoprost include ocular pruritus (up to 15%) and conjunctival hyperemia (up to 27%). Additional ocular adverse events noted in up to 10% of drug recipients include visual impairment or disturbance, blurred vision, foreign body sensation, ocular pain, ocular irritation, ocular burning, photophobia, conjunctival hemorrhage, increased intraocular pressure or ocular hypertension, corneal erosion or epithelial cell loss, iritis, blepharitis, cataracts, superficial punctate keratitis, xerophthalmia, and periorbital erythema. Adverse events reported in 1% to 5% of patients include anterior chamber cell, anterior chamber flare, anterior chamber inflammation, corneal touch, corneal edema, conjunctival edema, aqueous humor leakage, iris adhesions, erythema of the eyelid, eyelid pruritus, instillation site irritation, increased lacrimation, and reduced visual acuity. Events noted in 1% to 3% of patients include ocular discharge, allergic conjunctivitis, and asthenopia. Less than 1% of patients experienced an exacerbation of intraocular inflammation or ocular inflammation, hyphema, corneal opacification, corneal degeneration, iridocyclitis, and uveitis. Adverse events noted in postmarketing reports include eyelid edema, hordeolum, dry skin of the eyelid or periocular area, skin exfoliation of the eyelid or periorbital area, ocular swelling, ocular hemorrhage, and periorbital and lid changes associated with periorbital fat atrophy leading to skin tightness, deepening of the eyelid sulcus, eyelid ptosis, enophthalmos, and eyelid retraction.
Changes to pigmented tissue produced by bimatoprost include eyelash darkening (3% to 10%) and skin hyperpigmentation of the periocular skin (3% to 10%). Additionally, cases of non-periocular skin discoloration have been noted in postmarketing reports. Periorbital and eyelash pigment changes have been reported to be reversible upon treatment discontinuation. Iridal discoloration manifests as darkening of the iris and has been reported in 1% to 5% of patients. Pigmentation changes are caused by an increase in the amount of melanosomes in melanocytes rather than an increase in the number of melanocytes. The change in iris color occurs slowly and may not be noticeable for several months to years. The increase in brown iris pigment is not expected to progress further upon discontinuation of treatment, but the resultant color change may be permanent.
Macular edema (1% to 5%), including cystoid macular edema (less than 1%), has been reported during treatment with bimatoprost. Therefore, bimatoprost should be used with caution in aphakic patients, pseudophakic patients with a torn posterior lens capsule, and patients with known risk factors for macular edema.
Systemic adverse effects occurring in 1% to 5% of patients include asthenia, abnormal liver function tests, hirsutism, and headache. Dizziness, hypertension, and nausea have been reported during postmarketing use.
Asthma-like symptoms and dyspnea have been noted in postmarketing reports with bimatoprost.
Infection, primarily colds and upper respiratory tract infections, have been reported in about 10% of patients receiving bimatoprost.
Hypersensitivity reactions, including local allergic reactions, have been reported with the use of bimatoprost. Ocular allergy, allergic dermatitis, and rash, including maculopapular rash and erythematous rash, have been noted in postmarketing reports.
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.
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.
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.
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.
Safety and efficacy of the bimatoprost intracameral insert in pediatric patients have not been established. 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. 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.
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.
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 Limits:
-Adults
1 drop per 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 per 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 per 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 per 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.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustment in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustment 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 Bimatoprost products.
Mechanism of Action:-Reduction of intraocular pressure (IOP): Bimatoprost, a prostaglandin analog, is a synthetic structural analog of prostaglandin with ocular hypotensive activity. It selectively mimics the effects of naturally occurring substances, prostamides. Bimatoprost is believed to lower intraocular pressure (IOP) in humans by increasing outflow of aqueous humor through both the trabecular mesh work and uveoscleral routes. Elevated IOP presents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss.
-Promotion of eyelash growth: Bimatoprost is a structural prostaglandin analog. Although the precise mechanism of action is unknown, the growth of eyelashes is believed to occur by increasing the percent of hair follicles in the anagen or growth phase as well as prolonging the duration spent in this phase.
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
-Route-Specific Pharmacokinetics
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.