Bimatoprost

• Solution, Ophthalmic; 0.01%: Lumigan or Generic (2.5 mL, 5 mL, 7.5 mL)

• 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.

• Implant, Intracameral; 10mcg: Durysta (1 ea)

• 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.

• Solution, Ophthalmic; 0.03%: Latisse or Generic (3 mL, 5 mL)

• 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.

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

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

Pediatric

• 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.

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.

Geriatric

• No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

• Intraocular pressure
• Ocular pigmentation changes

• Hypersensitivity

• Ocular or periocular infections
• Corneal endothelial cell dystrophy
• Prior corneal transplantation
• Absent or ruptured posterior lens capsule
• Hypersensitivity

• Concurrent administration of bimatoprost ophthalmic solution and intraocular pressure (IOP)-lowering prostaglandin analogs in ocular hypertensive patients may decrease the IOP-lowering effect. Patients using these products concomitantly should be closely monitored for changes to their IOP
• Pigmentation of the iris, periorbital tissue (eyelid) and eyelashes can occur. Iris pigmentation is likely to be permanent.
• Gradual change to eyelashes including increased length, thickness and number of lashes. Usually reversible.

• Endothelial cell loss: Due to possible corneal endothelial cell loss, administration of DURYSTA should be limited to a single implant per eye without retreatment.
• Corneal Adverse Reactions: DURYSTA has been associated with corneal adverse reactions and risks are increased with multiple implants. Use caution in patients with limited corneal endothelial cell reserve.
• Iridocorneal Angle: DURYSTA should be used with caution in patients with narrow angles or anatomical angle obstruction.

• Most common adverse reactions are conjunctival hyperemia, eye pruritus, and skin hyperpigmentation.

• In controlled studies, the most common ocular adverse reaction reported by 27% of patients was conjunctival hyperemia. Other common adverse reactions reported in 5-10% of patients were foreign body sensation, eye pain, photophobia, conjunctival hemorrhage, dry eye, eye irritation, intraocular pressure increased, corneal endothelial cell loss, vision blurred, iritis, and headache.

• Summary

• 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

• No information is available on overdosage in humans. If overdose with LUMIGAN (bimatoprost ophthalmic solution) 0.01% occurs, treatment should be symptomatic. In oral (by gavage) mouse and rat studies, doses up to 100 mg/kg/day did not produce any toxicity. This dose expressed as mg/m² is at least 210 times higher than the accidental dose of one bottle of LUMIGAN 0.01% for a 10 kg child.

• Carcinogenesis

• Bimatoprost was not carcinogenic in either mice or rats when administered by oral gavage for 104 weeks at doses up to 2 mg/kg/day and 1 mg/kg/day, respectively (192 and 291 times the estimated human systemic exposure to bimatoprost 0.03% dosed bilaterally once daily, respectively, based on blood AUC levels, or approximately 3100 and 1700 times, respectively, the maximum human exposure to the implant )

• Mutagenesis

• Bimatoprost was not mutagenic or clastogenic in the Ames test, in the mouse lymphoma test, or in the in vivo mouse micronucleus tests.

• Impairment of fertility

• Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/kg/day (at least 103 times the recommended human exposure to bimatoprost 0.03% dosed bilaterally once daily based on blood AUC levels, or 1770-times the maximum human exposure to the implant ).

Potential for Pigmentation

• Advise patients about the potential for increased brown pigmentation of the iris, which may be permanent. Also inform patients about the possibility of eyelid skin darkening, which may be reversible after discontinuation of LUMIGAN (bimatoprost ophthalmic solution) 0.01%.

Potential for Eyelash Changes

• Inform patients of the possibility of eyelash and vellus hair changes in the treated eye during treatment with LUMIGAN 0.01%. These changes may result in a disparity between eyes in length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth. Eyelash changes are usually reversible upon discontinuation of treatment.

Handling the Container

• Instruct patients to avoid allowing the tip of the dispensing container to contact the eye, surrounding structures, fingers, or any other surface in order to avoid contamination of the solution by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.

When to Seek Physician Advice

• Advise patients that if they develop an intercurrent ocular condition (e.g., trauma or infection), have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions, they should immediately seek their physician’s advice concerning the continued use of LUMIGAN 0.01%.

Contact Lens Use

• Advise patients that LUMIGAN 0.01% contains benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of LUMIGAN 0.01% and may be reinserted 15 minutes following its administration.

Use with Other Ophthalmic Drugs

• Advise patients that if more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes between applications.

What is hypotrichosis of the eyelashes?

• Hypotrichosis is another name for having inadequate or not enough eyelashes.

What is bimatoprost ophthalmic solution?

• Bimatoprost ophthalmic solution is a prescription treatment for hypotrichosis used to grow eyelashes, making them longer, thicker and darker.

Who should NOT take bimatoprost ophthalmic solution?

• Do not use bimatoprost ophthalmic solution if you are allergic to one of its ingredients.

Are there any special warnings associated with bimatoprost ophthalmic solution use?

• Bimatoprost ophthalmic solution is intended for use on the skin of the upper eyelid margins at the base of the eyelashes. Refer to Illustration 2 below. DO NOT APPLY to the lower eyelid. If you are using Lumigan or other products in the same class for elevated intraocular pressure (IOP), or if you have a history of abnormal IOP, you should only use bimatoprost ophthalmic solution under the close supervision of your physician.
  Bimatoprost ophthalmic solution use may cause darkening of the eyelid skin which may be reversible. Bimatoprost ophthalmic solution use may also cause increased brown pigmentation of the colored part of the eye which is likely to be permanent.
  It is possible for hair growth to occur in other areas of your skin that bimatoprost ophthalmic solution frequently touches. Any excess solution outside the upper eyelid margin should be blotted with a tissue or other absorbent material to reduce the chance of this from happening. It is also possible for a difference in eyelash length, thickness, fullness, pigmentation, number of eyelash hairs, and/or direction of eyelash growth to occur between eyes. These differences, should they occur, will usually go away if youstop using bimatoprost ophthalmic solution.

Who should I tell that I am using bimatoprost ophthalmic solution?

• You should tell your physician you are using bimatoprost ophthalmic solution especially if you have a history of eye pressure problems. You should also tell anyone conducting an eye pressure screening that you are using bimatoprost ophthalmic solution.

What should I do if I get bimatoprost ophthalmic solution in my eye?

• Bimatoprost ophthalmic solution is an ophthalmic drug product. Bimatoprost ophthalmic solution is not expected to cause harm if it gets into the eye proper. Do not attempt to rinse your eye in this situation.

What are the possible side effects of bimatoprost ophthalmic solution?

• The most common side effects after using bimatoprost ophthalmic solution are an itching sensation in the eyes and/or eye redness. This was reported in approximately 4% of patients. Bimatoprost ophthalmic solution may cause other less common side effects which typically occur on the skin close to where bimatoprost ophthalmic solution is applied, or in the eyes. These include skin darkening, eye irritation, dryness of the eyes, and redness of the eyelids. If you develop a new ocular condition (e.g., trauma or infection), experience a sudden decrease in visual acuity, have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions, you should immediately seek your physician’s advice concerning the continued use of bimatoprost ophthalmic solution.

What happens if I stop using bimatoprost ophthalmic solution?

• If you stop using bimatoprost ophthalmic solution, your eyelashes are expected to return to their previous appearance over several weeks to months. Any eyelid skin darkening is expected to reverse after several weeks to months. Any darkening of the colored part of the eye known as the iris is NOT expected to reverse and is likely permanent.

How do I use bimatoprost ophthalmic solution?

• The recommended dosage is one application nightly to the skin of the upper eyelid margin at the base of the eyelashes only. Once nightly, start by ensuring your face is clean, makeup and contact lenses are removed. Remove an applicator from its tray. Then, holding the sterile applicator horizontally, place one drop of bimatoprost ophthalmic solution on the area of the applicator closest to the tip but not on the tip. Then immediately draw the applicator carefully across the skin of the upper eyelid margin at the base of the eyelashes (where the eyelashes meet the skin) going from the inner part of your lash line to the outer part. Blot any excess solution beyond the eyelid margin. Dispose of the applicator after one use. Repeat for the opposite upper eyelid margin using a new sterile applicator. This helps minimize any potential for contamination from one eyelid to another.
  DO NOT APPLY in your eye or to the lower lid. ONLY use the sterile applicators supplied with bimatoprost ophthalmic solution to apply the product. If you miss a dose, don’t try to “catch up”. Just apply bimatoprost ophthalmic solution the next evening. Fifty percent of patients treated with bimatoprost ophthalmic solution in a clinical study saw significant improvement by 2 months after starting treatment. If any bimatoprost ophthalmic solution gets into the eye proper, it is not expected to cause harm. The eye should not be rinsed. Don’t allow the tip of the bottle or applicator to contact surrounding structures, fingers, or any other unintended surface in order to avoid contamination by common bacteria known to cause infections. Contact lenses should be removed prior to application of bimatoprost ophthalmic solution and may be reinserted 15 minutes following its administration. Use of bimatoprost ophthalmic solution more than once a day will not increase the growth of eyelashes more than use once a day. Store bimatoprost ophthalmic solution at 36° to 77°F (2° to 25°C).

What are the ingredients in bimatoprost ophthalmic solution?

• Active ingredient: bimatoprost. Inactive ingredients: benzalkonium chloride, citric acid, purified water, sodium chloride and sodium phosphate dibasic. Sodium hydroxide and/or hydrochloric acid may be added to adjust pH. The pH during its shelf life ranges from 6.8 to 7.8.

Treatment-related Effects:

• Advise patients about the potential risk for complications including, but not limited to, the development of corneal adverse events, intraocular inflammation or endophthalmitis

Potential for Pigmentation:

• Advise patients about the potential for increased brown pigmentation of the iris, which may be permanent.

When to Seek Physician Advice?

• Advise patients that if the eye becomes red, sensitive to light, painful, or develops a change in vision, they should seek immediate care from an ophthalmologist.

• Bimatoprost ophthalmic solution 0.01%
• Bimatoprost ophthalmic solution 0.03%
• Bimatoprost intracameral implant 10mcg

American Academy of Ophthalmology 2020

• Gedde SJ, Vinod K, Wright MM, et al. Primary Open-Angle Glaucoma Preferred Practice Pattern®. Ophthalmology. 2021;128(1):P71-P150. doi:10.1016/j.ophtha.2020.10.022