Bimatoprost - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

Overview

Bimatoprost ophthalmic solution is an eye drop medicine used to treat high ocular pressure in open-angle glaucoma and ocular hypertension. It is also used cosmetically to treat hypotrichosis. Bimatoprost allows the fluid to flow from the inside of the eye into the blood. Excess ocular pressure can damage the eye leading to blindness if left untreated. Therefore, Bimatoprost is used in treating open-angle glaucoma, especially in cases where other agents have failed to produce satisfactory results.

Bimatoprost ophthalmic solution is available under the trade name Lumigan. It was approved for use by the US FDA (United States Food and Drug Administration) on the 16th of March 2001. In 2008, the FDA also approved its use for treating hypotrichosis (reduced eyelashes) in patients post-chemotherapy. As one of the effects of Bimatoprost is the formation of longer, darker, and thicker eyelashes, it is also used for cosmetic purposes. In 2015, generic Bimatoprost became available.

How Does Bimatoprost Work?

Bimatoprost is an FP prostaglandin receptor agonist. It is a synthetic structural analog of prostaglandin F2alpha. Bimatoprost is labeled as a prostamide because it is an amide, not an ester.

Reduction of Intraocular Pressure:

Bimatoprost and other prostaglandin analogs reduce intraocular pressure. They are the first line of treatment for primary open-angle glaucoma. This occurs due to aqueous outflow through the uveoscleral pathway. Bimatoprost enhances matrix metalloproteinase (MMP) levels in the sclera and ciliary muscles. These MMPs induce collagen decomposition in the extracellular matrix, leading to improved uveoscleral outflow. Few studies suggest that Bimatoprost promotes trabecular outflow along with uveoscleral outflow. Therefore, lowering intraocular pressure in glaucoma and intraocular hypertension patients can slow disease progression.

Enhancement of Eyelash Growth:

A series of studies in which Bimatoprost was used for two weeks showed a significant portion of hair follicles in the anagen phase and a decrease in the telogen phase. This suggested a transition from telogen to anagen. An increased proportion of hair follicles in the anagen phase points toward an increase in the growth of eyelashes with Bimatoprost use. This occurs due to the outer root sheath of the dermal papilla.

Indications and Uses:

0.01 percent and 0.03 percent Bimatoprost ophthalmic solution reduces elevated intraocular pressure in patients with open-angle glaucoma and ocular hypertension. When used to reduce intraocular pressure, Bimatoprost can be used alone or concurrently with other medicines like Timolol. 0.01 percent Bimatoprost had less severe and frequent adverse effects, making it the most commonly used dosage in the United States.

How Is Bimatoprost Administered?

• The recommended dosage of Bimatoprost is one drop in each eye, administered once daily in the evening.

• Both 0.01 percent and 0.03 percent should not be administered more than once daily, as frequent prostaglandin analogs can lead to significantly reduced intraocular pressure.

• Reduction in intraocular pressure begins after four hours and peaks at eight to twelve hours.

• Bimatoprost can also be used concurrently with other topical ophthalmic products. In such cases, both products can be used five minutes apart.

The administration of Bimatoprost ophthalmic solution varies according to the intended effects.

Bimatoprost Ophthalmic Solution for Open-Angle Glaucoma:

0.01 percent and 0.03 percent Bimatoprost ophthalmic solution can be used directly by the ocular application. The dosage is one drop every evening. If used along with other ophthalmic products, a minimum of a five-minute gap must be maintained between both doses. 0.03 percent Bimatoprost starts reducing the intraocular pressure after four hours of administration and peaks by 12 hours. The effect is maintained for 24 hours. Bimatoprost is relatively safe and can be used for the long term.

Bimatoprost Ophthalmic Solution for Hypotrichosis:

Bimatoprost 0.03 percent can also be used for the cosmetic purpose of improving the prominence of eyelashes. It is available in bottles with an included applicator tip. Contact lenses, if any, should be removed before application. It is not recommended to apply the solution directly to the eye. Instead, every evening the single-use per-eye applicator must be used to apply a drop of the solution directly to the base of the upper eyelid. The single-use applicator reduces the risk of contamination. Studies suggest that it takes at least 16 weeks to attain maximum eyelash prominence.

Bimatoprost Implant for Open-Angle Glaucoma:

Though Bimatoprost effectively reduces intraocular pressure, factors like improper patient adherence can impact treatment outcomes. Frequent dosing, improper medicine administration, forgetfulness, or adverse effects can be the barriers.

To overcome such concerns, the Bimatoprost sustained-release implant was developed and used in 2020 in the United States. It is a sterile, single rod-shaped polymer containing 10 to 15 micrograms of Bimatoprost. It is preloaded into a single-use applicator and injected into the anterior chamber. The implant delivers the medicine into the iris-ciliary body. Studies have shown that implants, when administered on day 1, week 16, and week 32 worked, and there was no need for additional treatment for 12 months.

Dosage Forms and Strengths:

Bimatoprost ophthalmic solution is available in two dosage forms:

1. 0.01 percent (0.1 mg/mL Bimatoprost).

2. 0.03 percent (0.3 mg/mL Bimatoprost).

What Are the Contraindications of Bimatoprost?

The medication is contraindicated in the below cases:

1. Patients with a history of hypersensitivity to Bimatoprost or other ingredients in the formulation, like benzalkonium chloride (preservative).

2. The drug use may not be appropriate in a few cases of closed-angle glaucoma, neovascular or inflammatory glaucoma.

3. Intraocular use of Bimatoprost is contraindicated in neonates, infants, and children below the age of five due to pigmentation concerns with long-term use.

What Are the Drug Warnings and Precautions?

Pigmentation:

Bimatoprost can cause pigmentation in specific tissues due to increased melanin content in the melanocytes. There were reported cases of increased pigmentation of the iris, eyelashes, and periorbital tissues. However, the pigmentation of the periorbital tissues and eyelashes was reversible after the discontinuation of the drug, whereas iris pigmentation was permanent. Therefore, patients must be informed in advance about pigmentation. Iris pigmentation is noticeable after several months to years of Bimatoprost use. Patients with nevi or freckles must be examined regularly.

Eyelash Changes:

Thicker, darker, and lengthier eyelashes have been observed in patients using Bimatoprost. However, these effects are reversed when the drug is discontinued.

Intraocular Inflammation:

Bimatoprost must be used cautiously in patients with uveitis (intraocular inflammation), as the inflammation can be exacerbated.

Macular Edema:

Cases of macular edema, particularly cystic macular edema, have been reported with Bimatoprost use. Therefore, the medication must be used with caution in patients with a history of macular edema, aphakic patients, and pseudophakic patients with a torn posterior lens capsule.

Angle-Closure, Inflammatory, and Neovascular Glaucoma:

The use of Bimatoprost for angle closure, inflammatory, and neovascular glaucoma has not been evaluated.

Bacterial Keratitis:

Cases of bacterial keratitis have been reported using multiple containers of ophthalmic solutions. Patients with corneal disease or ocular complaints who inadvertently contaminate the solutions can be affected with bacterial keratitis.

Use of Contact Lenses:

Contact lenses must be removed before the instillation of Bimatoprost eye drops and can be reinserted after 15 minutes.

What Are the Adverse Reactions of Bimatoprost?

Bimatoprost has a high level of safety when applied to the ocular surfaces. Apart from the growth of eyelashes, the other possible adverse effects of the drug included.

• Conjunctival hyperemia (25 percent to 45 percent).

• Eye pruritis (9 percent).

• Burning irritation.

• Dry eye syndrome.

• Visual disturbances.

• Eye pain.

• Pigmentation of the margins of eyelids.

• Foreign body sensations.

• Periorbitopathy (associated with mild ptosis, deepening of the sulcus of upper eyelids, and periorbital fat atrophy).

• Cystoid macular edema (CME).

• Blepharitis.

• Cataract.

• Eye discharge.

• Photophobia.

• Superficial punctate keratitis.

• Allergic conjunctivitis.

• Asthenopia.

• Conjunctival edema and hemorrhage.

• Abnormal hair growth.

• Re exacerbation of anterior non-granulomatous uveitis (rare side effect).

Systemic side effects reported in about 10 percent of patients were:

• Upper respiratory tract infections.

• Headaches.

• Asthenia.

• Abnormal liver function tests.

Recent studies have suggested that dermal application of Bimatoprost ophthalmic solution has fewer adverse effects when compared to eye application, with less than 4 percent of adverse effects being reported.

Use in Specific Populations:

Pregnancy:

There have been adverse effects like teratogenic effects and abortions in pregnant mice and rats when administered with Bimatoprost ophthalmic solutions. There is no evidence about the use of the drug in pregnant women. Therefore, drug use must be considered only if the potential benefits outweigh the risks.

Nursing Mothers:

There is no evidence whether Bimatoprost is excreted in human milk. However, as most drugs are excreted in human milk, the medication must be prescribed with caution in breastfeeding mothers.

Pediatric Use:

Bimatoprost is not recommended in pediatric patients below the age of 16 due to potential safety concerns. There can be increased pigmentation with chronic long-term use.

Geriatric Use:

There was no difference in the safety and effectiveness of the drug when used in geriatric patients and other adult patients.

Hepatic Impairment:

In patients with liver disease or AST (aspartate transaminase), ALT (alanine transaminase), and bilirubin at baseline levels, there have been no adverse effects, with 0.03 percent Bimatoprost causing liver dysfunction when used over 48 months.

Overdosage:

There is no documented information about the overdosage of Bimatoprost. However, in cases of overdosage, symptomatic treatment must be considered.

For Patients:

What Is Glaucoma, and How Is It Managed?

Glaucoma is an eye condition that increases the pressure in the eye (intraocular pressure). This, in turn, can damage the optic nerve, which sends signals from the eye to the brain. The condition is common in older adults and is the reason for blindness in people above 60. Sometimes, there are no symptoms in the early stages, and they are detected when the condition becomes advanced. An early start of treatment can slow or prevent vision loss. However, the patients require monitoring and treatment for the rest of their lives.

Glaucoma is managed through eye drops, oral medications, or surgery. They belong to different categories based on how they work. Bimatoprost, a prostaglandin, increases the fluid outflow from the eye, whereas beta blockers, alpha-adrenergic agonists, and carbonic anhydrase inhibitors decrease fluid production. Various surgical options include laser therapy, filtering surgery, and drainage tubes.

For Doctors:

Description:

Bimatoprost ophthalmic solution (0.01 percent and 0.03 percent) is a synthetic prostamide analog. It produces an ocular hypotensive activity. Bimatoprost is a powder highly soluble in ethyl alcohol and methyl alcohol and is moderately soluble in water. It is a clear, colorless, isotonic, sterile ophthalmic solution with an osmolality of 290 mOsmol/kg.

Chemical Name:

(Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(1E,3S)- 3-hydroxy-5-phenyl-1-pentenyl]cyclopentyl]-5-Nethylheptenamide.

Molecular Weight:

415.58.

Molecular Formula:

C25H37NO4

Active Ingredient:

Biatoprost.

Inactive Ingredients:

• Sodium Chloride.

• Sodium phosphate, dibasic.

• Citric acid.

• Purified water.

Preservatives:

Benzalkonium chloride.

Sodium hydroxide or hydrochloric acid can be added to adjust the pH. The pH during shelf life is between 6.8 to 7.8.

Clinical Pharmacology:

Mechanism of Action:

Bimatoprost is a prostaglandin analog. It is a synthetic structural analog of prostaglandin and has ocular hypotensive activity. It selectively mimics the effects of prostamides, which are naturally occurring substances. Bimatoprost lowers the intraocular pressure by increasing the outflow of aqueous humor through uveoscleral routes and trabecular meshwork. Elevated intraocular pressure is a risk factor for field loss in glaucoma patients. The higher the intraocular pressure, the greater the chances for optic nerve damage and visual field loss.

Pharmacokinetics:

Absorption:

After one drop of 0.03 percent, Bimatoprost ophthalmic solution was administered to both eyes in 15 healthy subjects for two weeks; blood concentrations of the drug peaked within ten minutes and were lower than the limit of detection, i.e., 0.025 ng/mL in most patients after one and a half hours. C max (maximum concentration that a drug reaches in the body) and AUC (area under the curve) values indicated that a steady state was reached during the first week of dosing. Over time, there was no significant systemic accumulation of the drug.

Distribution:

Bimatoprost is moderately distributed in the body tissues. Therefore, the drug resides mainly in the plasma. However, around 12 percent of the drug remains unbound in human plasma.

Metabolism:

Bimatoprost is the primary circulating drug once it reaches blood following ocular administration. Then, it undergoes oxidation, N-demethylation, and glucuronidation to form different metabolites.

Elimination:

During the intravenous administration of radiolabeled Bimatoprost, it was observed that about 67 percent was excreted in the urine, and 25 percent was recovered from feces.

Monitoring:

During the initial phases of Bimatoprost administration, the patient must be monitored every two to four weeks until the goal of optimal intraocular pressure for that particular patient is achieved. After reaching the plan, the patient can be monitored every six months. Ocular and periocular pigmentation changes must also be observed. As Bimatoprost can cause the growth of eyelashes, potential side effects must be monitored simultaneously.

Non-Clinical Toxicology:

Carcinogenesis, Mutagenesis, and Impairment of Fertility:

Studies on rats and mice have demonstrated no evidence of carcinogenesis, mutagenesis, and fertility impairment.

Clinical Studies:

Clinical studies were conducted on patients with open-angle glaucoma and ocular hypertension with IOP (intraocular pressure) in the range of 26 mmHg. When administered 0.03 percent Bimatoprost once daily, these patients were reduced to 7 to 8 mmHg.

In a three-month clinical study, administering 0.01 percent Bimatoprost in patients with a baseline IOP of 23.5 mmHg was reduced to 7 to 8 mmHg. 0.01 percent Bimatoprost was 0.5 mmHg less effective than 0.03 percent. The same study also revealed that both 0.01 percent and 0.03 percent of Bimatoprost had a similar safety profile. After 12 months, discontinuation for 0.01 percent was 8.1 percent, and for 0.03 percent was 13.4 percent.

Supply, Storage, and Handling:

Bimatoprost 0.01 percent is supplied in sterile, white, opaque, low-density polyethylene dispenser bottles and tips having polystyrene turquoise caps. They are available in the following sizes:

1. 1 mL fill in a 5 mL container.

2. 2.5 mL fill in a 5 mL container.

3. 5 mL fill in a 10 mL container.

4. 7.5 mL fill in a 10 mL container.

Bimatoprost 0.03 percent is supplied in sterile, white, opaque, low-density polyethylene dispenser bottles and tips having polystyrene turquoise caps. They are available in the following sizes:

1. 2.5 mL fill in a 5 mL container.

2. 5 mL fill in a 10 mL container.

3. 7.5 mL fill in a 10 mL container.

Bimatoprost 0.01 percent and 0.03 percent must be stored at 2 to 25 degrees Celsius. (36 to 77 degrees Fahrenheit).

Patient Counseling Information:

Potential for Pigmentation:

Patients must be informed about the pigmentation of the iris with Bimatoprost use that can be permanent and darkening of the skin of eyelids, which reverses on stopping the medication.

Potential for Eyelash Development:

Patients must be informed about the development of longer, thicker, and darker eyelashes, with varying growth direction that reverses upon discontinuation of the drug.

Handling the Container:

Patients must be instructed about maintaining hygiene while using the container. They must avoid touching the dispenser tip directly on the surface of the eye, fingertips, or other surfaces. Improper usage can increase the risk of bacterial infections that can damage the eye or cause vision loss.

When to Seek a Physician’s Advise:

If a patient develops an ocular infection, trauma, or eye condition, during the use of Bimatoprost, a physician's advice must be sought about the continuation of Bimatoprost.

Use of Contact Lenses:

Bimatoprost 0.01 percent and 0.03 percent contain benzalkonium chloride, which soft contact lenses can absorb. Therefore, patients must be advised to remove the lenses five minutes prior instillation of Bimatoprost which can be worn after 15 minutes.

Use With Other Ophthalmic Solutions:

If Bimatoprost and other ophthalmic solutions are being used concurrently, it is recommended to maintain a gap of at least five minutes between both doses.