Durysta

Description

DURYSTA is a sterile intracameral implant that contains 10 mcg of bimatoprost, a prostaglandin analog, within a solid polymer sustained-release drug delivery system (DDS). The DDS is composed of poly (D,L-lactide), poly (D,L-lactide-co-glycolide), poly (D,L-lactide) acid end, and polyethylene glycol 3350. This implant is preloaded into a single-use DDS applicator, designed to facilitate the injection of the rod-shaped implant directly into the anterior chamber of the eye.

The chemical name of bimatoprost is (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-(1E,3S)-3-hydroxy-5-phenyl-1-pentenylcyclopentyl]-N-ethyl-5-heptenamide, with a molecular weight of 415.57 and a molecular formula of C25H37NO4. Bimatoprost appears as a white to off-white powder, exhibiting solubility in ethyl alcohol and methyl alcohol, while being slightly soluble in water. The polymer matrix of the implant gradually degrades into lactic acid and glycolic acid.

Uses and Indications

DURYSTA is a prostaglandin analog indicated for the reduction of intraocular pressure (IOP) in patients with open angle glaucoma (OAG) or ocular hypertension (OHT).

There are no teratogenic or nonteratogenic effects associated with this drug.

Dosage and Administration

Ophthalmic intracameral administration is to be performed under standard aseptic conditions to ensure patient safety and minimize the risk of infection. Healthcare professionals should adhere to established protocols for preparation and administration to maintain sterility throughout the procedure.

Contraindications

Use of this product is contraindicated in patients with ocular or periocular infections due to the potential for exacerbation of the condition. It is also contraindicated in individuals with corneal endothelial cell dystrophy, as this may lead to further complications. Prior corneal transplantation is a contraindication due to the risk of graft rejection or failure. The presence of an absent or ruptured posterior lens capsule contraindicates use, as it may compromise ocular integrity. Additionally, hypersensitivity to any component of the product is a contraindication, as it may result in adverse reactions.

Warnings and Precautions

Administration of DURYSTA is associated with specific warnings and precautions that healthcare professionals must consider to ensure patient safety.

Endothelial Cell Loss Due to the potential for corneal endothelial cell loss, the use of DURYSTA should be restricted to a single implant per eye. Retreatment with additional implants is not recommended.

Corneal Adverse Reactions DURYSTA has been linked to corneal adverse reactions, with the risk of such reactions increasing with the use of multiple implants. Caution is advised when administering DURYSTA to patients who have a limited reserve of corneal endothelial cells.

Iridocorneal Angle Considerations Healthcare professionals should exercise caution when prescribing DURYSTA to patients with narrow angles or anatomical obstructions of the angle, as these conditions may exacerbate the risks associated with the treatment.

It is essential for healthcare providers to remain vigilant regarding these warnings and to assess each patient's individual risk factors before proceeding with treatment.

Side Effects

Patients receiving DURYSTA may experience a range of adverse reactions, which can be categorized by frequency and seriousness.

Common ocular adverse reactions, occurring in 5-10% of patients, include conjunctival hyperemia (27%), foreign body sensation, eye pain, photophobia, conjunctival hemorrhage, dry eye, eye irritation, increased intraocular pressure, corneal endothelial cell loss, blurred vision, and iritis.

Ocular adverse reactions reported in 1-5% of patients consist of anterior chamber cells, increased lacrimation, corneal edema, aqueous humor leakage, iris adhesions, ocular discomfort, corneal touch sensitivity, iris hyperpigmentation, anterior chamber flare, anterior chamber inflammation, and macular edema.

Less common ocular adverse reactions, occurring in less than 1% of patients, include hyphema, iridocyclitis, uveitis, corneal opacity, corneal thickening, inappropriate site administration of the product, corneal decompensation, cystoid macular edema, and drug hypersensitivity.

Additionally, a common nonocular adverse reaction noted in 5% of patients is headache.

Postmarketing experience has revealed cases of endophthalmitis associated with DURYSTA.

It is important to note that due to the potential for corneal endothelial cell loss, administration of DURYSTA should be limited to a single implant per eye without retreatment. The risk of corneal adverse reactions is heightened with multiple implants, necessitating caution in patients with limited corneal endothelial cell reserve. DURYSTA should also be used with caution in patients with narrow angles or anatomical angle obstruction, as well as those with ocular or periocular infections, corneal endothelial cell dystrophy, prior corneal transplantation, absent or ruptured posterior lens capsule, and hypersensitivity.

Drug Interactions

There are no specific drug interactions or laboratory test interactions identified in the available data. Therefore, no recommendations for dosage adjustments or monitoring are necessary at this time.

Packaging & NDC

The table below lists all NDC Code configurations of Durysta (bimatoprost), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Safety and effectiveness of DURYSTA in pediatric patients have not been established. There are currently no available data to support its use in children or adolescents. Therefore, caution is advised when considering treatment options for this population.

Geriatric Use

Elderly patients, defined as those aged 65 years and older, have not demonstrated any overall differences in safety or effectiveness compared to younger adult patients. Therefore, no specific dosage adjustments are necessary for this population.

However, it is essential for healthcare providers to remain vigilant when prescribing to geriatric patients, as individual responses may vary. Continuous monitoring for any potential adverse effects or changes in therapeutic response is recommended to ensure optimal treatment outcomes.

Pregnancy

There are no adequate and well-controlled studies of DURYSTA (bimatoprost intracameral implant) administration in pregnant women to inform a drug-associated risk. Animal studies have provided some insights into the effects of bimatoprost during pregnancy. Oral administration of bimatoprost to pregnant rats and mice throughout organogenesis did not produce adverse maternal or fetal effects at clinically relevant exposures. However, in an embryofetal development study in rats, administration of bimatoprost during organogenesis resulted in abortion at a dose of 0.6 mg/kg/day, which is approximately 1770 times the human systemic exposure to bimatoprost from DURYSTA, based on Cmax and a blood-to-plasma partition ratio of 0.858. The No Observed Adverse Effect Level (NOAEL) for abortion in this study was determined to be 0.3 mg/kg/day, estimated at 470 times the human systemic exposure.

Similarly, in a mouse study, oral administration of bimatoprost during organogenesis led to abortion and early delivery at a dose of 0.3 mg/kg/day, approximately 2240 times the human systemic exposure. The NOAEL for abortion and early delivery in mice was 0.1 mg/kg/day, estimated at 400 times the human systemic exposure. Notably, no fetal abnormalities were observed in either species at doses up to 0.6 mg/kg/day.

In a pre/postnatal development study, oral administration of bimatoprost to pregnant rats from gestation day 7 through lactation resulted in reduced gestation length, increased late resorptions, fetal deaths, and postnatal pup mortality, as well as reduced pup body weight at a dose of 0.3 mg/kg/day, estimated at 470 times the human systemic exposure. No adverse effects were observed in rat offspring at a dose of 0.1 mg/kg/day, estimated at 350 times the human systemic exposure.

Given the potential risks observed in animal studies, healthcare professionals should weigh the benefits and risks of DURYSTA in pregnant patients and consider alternative treatments when necessary. Women of childbearing potential should be advised to use effective contraception during treatment with DURYSTA.

Lactation

There is no information regarding the presence of bimatoprost in human milk, the effects on breastfed infants, or the effects on milk production. However, animal studies indicate that topical bimatoprost is excreted in breast milk.

Given that many drugs are excreted in human milk, caution should be exercised when DURYSTA is administered to lactating mothers. The developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for DURYSTA and any potential adverse effects on the breastfed child from the medication.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available prescribing information. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function. Healthcare professionals should exercise caution and consider the lack of data when prescribing to this patient population.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

In the absence of specific information regarding overdosage, healthcare professionals are advised to exercise caution and adhere to general principles of management in cases of suspected overdose.

It is essential to monitor the patient closely for any potential symptoms that may arise from an overdose. Symptoms can vary widely depending on the substance involved and the individual patient's response.

In the event of an overdose, immediate medical attention should be sought. Healthcare providers should implement standard supportive care measures, which may include maintaining airway patency, providing supplemental oxygen, and monitoring vital signs.

Additionally, it is recommended to consult local poison control centers or relevant toxicology resources for guidance on specific management protocols and antidotes, if applicable.

Documentation of the incident, including the substance involved, estimated dose, and time of exposure, is crucial for effective management and follow-up care.

Nonclinical Toxicology

Bimatoprost was evaluated for its potential carcinogenic effects in long-term studies conducted in mice and rats. The results indicated that bimatoprost was not carcinogenic when administered via oral gavage at doses of up to 2 mg/kg/day in mice and 1 mg/kg/day in rats for a duration of 104 weeks. These doses correspond to approximately 3100 and 1700 times the maximum human exposure based on plasma Cmax levels, considering a blood-to-plasma partition ratio of 0.858.

In terms of mutagenicity, bimatoprost demonstrated no mutagenic or clastogenic effects in a series of tests, including the Ames test, the mouse lymphoma test, and in vivo mouse micronucleus assays.

Furthermore, bimatoprost did not impair fertility in male or female rats at doses up to 0.6 mg/kg/day, which is approximately 1770 times the maximum human exposure based on plasma Cmax levels, again taking into account the blood-to-plasma partition ratio of 0.858.

Postmarketing Experience

During postapproval use of DURYSTA, the following adverse reactions have been identified. These reactions are reported voluntarily from a population of uncertain size, making it challenging to reliably estimate their frequency or establish a causal relationship to drug exposure.

Eye Disorders

• Endophthalmitis

Patient Counseling

Healthcare providers should advise patients about the potential risks associated with their treatment, including the possibility of complications such as corneal adverse events, intraocular inflammation, or endophthalmitis. It is important for patients to understand these risks to ensure they are vigilant about their eye health.

Additionally, healthcare providers should inform patients about the potential for increased brown pigmentation of the iris, which may be a permanent change. Patients should be made aware of this possibility to manage their expectations regarding cosmetic outcomes.

Providers should also emphasize the importance of seeking immediate care from an ophthalmologist if patients experience any concerning symptoms. Specifically, patients should be instructed to contact their healthcare provider if they notice redness in the eye, increased sensitivity to light, pain, or any changes in vision. Prompt attention to these symptoms is crucial for maintaining eye health and preventing serious complications.

Storage and Handling

DURYSTA is supplied as a single-use applicator containing a 10 mcg bimatoprost intracameral implant. Each applicator is packaged in a sealed foil pouch that includes a desiccant to maintain product stability.

For optimal storage, DURYSTA must be refrigerated at a temperature range of 2°C to 8°C (36°F to 46°F). It is essential to handle the product with care to ensure its integrity and effectiveness.

Additional Clinical Information

During postmarketing surveillance of DURYSTA, an adverse reaction identified is endophthalmitis, categorized under eye disorders. It is important to note that these reactions are reported voluntarily from a population of uncertain size, making it challenging to reliably estimate their frequency or establish a causal relationship to the drug exposure.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Durysta as submitted by Allergan, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)