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Drugs & Aging Jun 2020Bimatoprost implant (Durysta™), developed by Allergan, is a sustained-release drug delivery system containing bimatoprost, a prostaglandin analogue with ocular... (Review)
Review
Bimatoprost implant (Durysta™), developed by Allergan, is a sustained-release drug delivery system containing bimatoprost, a prostaglandin analogue with ocular hypotensive activity. The implant, administered intracamerally, involves the use of a biodegradable, solid polymer drug delivery system for slow, sustained drug release, designed to lower intraocular pressure (IOP) over a 4- to 6-months period. In March 2020, bimatoprost implant received its first approval, in the USA, for use to reduce IOP in patients with open angle glaucoma (OAG) or ocular hypertension (OHT). Allergan's clinical development programme for bimatoprost implant is ongoing. This article summarizes the milestones in the development of bimatoprost implant leading to this first approval for use in the reduction of IOP in patients with OAG or OHT.
Topics: Bimatoprost; Drug Approval; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Prostheses and Implants
PubMed: 32447639
DOI: 10.1007/s40266-020-00769-8 -
Seminars in Ophthalmology Apr 2022Sustained release drug delivery has the potential to change glaucoma care by decreasing the challenge of medication adherence. Many approaches are in development, but... (Review)
Review
BACKGROUND
Sustained release drug delivery has the potential to change glaucoma care by decreasing the challenge of medication adherence. Many approaches are in development, but this review focuses on Durysta (Allergan plc, Dublin, Ireland), the only FDA-approved sustained release intracameral treatment available at this time.
KEY FINDINGS
Durysta is a bimatoprost sustained release (BimSR) intracameral implant. Clinical trials have demonstrated that BimSR implants can provide comparable levels of intraocular pressure (IOP) control as topical eyedrops. BimSR has advantages such as decreasing concerns regarding drop adherence, reducing ocular surface and periocular side effects from topical drops, and decreased daily treatment burden for patients. In addition, studies have shown continued IOP lowering in some eyes during extended follow-up periods when all of the BimSR medication has already been delivered. Hypothesized mechanisms to explain this finding include increased matrix metalloproteinase expression that causes extracellular matrix reorganization to permit greater aqueous outflow, as well as decreased episcleral venous pressure. The major safety concern at this time for Durysta and future intracameral implants is corneal endothelial cell loss, which was worse with repeat BimSR administration compared to single dosing. Several studies are underway to investigate mechanisms of action and to better understand safe and effective dosing of medications in this class.
Topics: Antihypertensive Agents; Bimatoprost; Delayed-Action Preparations; Humans; Injections, Intraocular; Intraocular Pressure; Ocular Hypertension
PubMed: 34586961
DOI: 10.1080/08820538.2021.1985145 -
Ophthalmology Dec 2020To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10- and 15-μg bimatoprost implant in subjects with open-angle glaucoma (OAG) and ocular... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10- and 15-μg bimatoprost implant in subjects with open-angle glaucoma (OAG) and ocular hypertension (OHT) after initial and repeated administrations.
DESIGN
Randomized, 20-month, multicenter, subject- and efficacy evaluator-masked, parallel-group, phase 3 clinical study.
PARTICIPANTS
Adults with OAG or OHT in each eye, open iridocorneal angle inferiorly in the study eye, and study eye baseline IOP (hour 0; 8 am) of 22-32 mmHg after washout.
METHODS
Study eyes received bimatoprost implant 10 μg (n = 198) or 15 μg (n = 198) on day 1 with readministration at weeks 16 and 32, or twice-daily topical timolol maleate 0.5% (n = 198). Intraocular pressure was measured at hours 0 and 2 at each visit.
MAIN OUTCOME MEASURES
Primary end points were IOP and change from baseline IOP through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD).
RESULTS
Both dose strengths of bimatoprost implant were noninferior to timolol in IOP lowering after each administration. Mean diurnal IOP was 24.0, 24.2, and 23.9 mmHg at baseline and from 16.5-17.2, 16.5-17.0, and 17.1-17.5 mmHg through week 12 in the 10-μg implant, 15-μg implant, and timolol groups, respectively. The incidence of corneal and inflammatory TEAEs of interest (e.g., corneal endothelial cell loss, iritis) was higher with bimatoprost implant than timolol and highest with the 15-μg dose strength. Incidence of corneal TEAEs increased after repeated treatment; with 3 administrations at fixed 16-week intervals, incidence of ≥20% CECD loss was 10.2% (10-μg implant) and 21.8% (15-μg implant). Mean best-corrected visual acuity (BCVA) was stable; 3 implant-treated subjects with corneal TEAEs had >2-line BCVA loss at their last visit.
CONCLUSIONS
Both dose strengths of bimatoprost implant met the primary end point of noninferiority to timolol through week 12. One year after 3 administrations, IOP was controlled in most subjects without additional treatment. The risk-benefit assessment favored the 10-μg implant over the 15-μg implant. Ongoing studies are evaluating other administration regimens to reduce the potential for CECD loss. The bimatoprost implant has potential to improve adherence and reduce treatment burden in glaucoma.
Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Bimatoprost; Double-Blind Method; Drug Implants; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Timolol; Tonometry, Ocular; Vitreous Body; Young Adult
PubMed: 32544560
DOI: 10.1016/j.ophtha.2020.06.018 -
Expert Opinion on Investigational Drugs Apr 2017Alopecia is a common condition observed among people of all ages. It is a disorder that can involve only the scalp as observed in androgenetic alopecia or scalp and body... (Review)
Review
Alopecia is a common condition observed among people of all ages. It is a disorder that can involve only the scalp as observed in androgenetic alopecia or scalp and body as in alopecia areata or patients under chemotherapy treatment. There are several treatment options with different safety and efficacy outcomes. Bimatoprost, a synthetic prostamide F2α analog originally approved for the treatment of ocular hypertension and open-angle glaucoma, is now FDA approved as a 0.03%, solution to be applied once daily to increase eyelashes growth. Areas covered: In this review, the authors evaluate the role of bimatoprost in idiopathic hypotrichosis of the eyelashes, in hypotrichosis of the eyelashes associated to chemotherapy, in alopecia areata of the eyelashes and eyebrows and in androgenetic alopecia. In addition, pharmacokinetics, pharmacodynamics, safety and tolerability of bimatoprost are discussed. Expert opinion: Bimatoprost will likely be the third FDA approved weapon in the fight against hair loss. Prostaglandin analogs are the only possible treatment for hypotrichosis and alopecia of the eyelashes regardless of its etiology. Eyebrow hypotrichosis due to alopecia areata or frontal fibrosis alopecia can also possibly benefit of these medications.
Topics: Alopecia; Bimatoprost; Eyebrows; Eyelashes; Humans; Hypotrichosis; Scalp
PubMed: 28264599
DOI: 10.1080/13543784.2017.1303480 -
Drug Design, Development and Therapy 2018Eyebrows serve as a key feature of the face and have many roles, including cosmetic appearance and social communication. Eyebrow hypotrichosis, which refers to reduction... (Review)
Review
Eyebrows serve as a key feature of the face and have many roles, including cosmetic appearance and social communication. Eyebrow hypotrichosis, which refers to reduction or absence of the eyebrow hair, could be a major problem that leads to negative functional, psychological, and social consequences. Bimatoprost is an ophthalmic prostamide analog that is approved by the United States Food and Drug Administration for the treatment of eyelash hypotrichosis. Its proposed mechanism is stimulation of the prostaglandin receptor in dermal papilla and melanocyte, thus leading to a prolonged anagen phase and increased melanogenesis. The hair follicle then increases in thickness, length, and darkness. The efficacy of bimatoprost for the treatment of eyebrow hypotrichosis has been supported by well-controlled studies. Bimatoprost, which is noninvasive, effective, and well tolerated, is worth considering as a treatment option for eyebrow hypotrichosis.
Topics: Bimatoprost; Eyebrows; Hair Follicle; Humans; Hypotrichosis; Receptors, Prostaglandin; Treatment Outcome
PubMed: 29503529
DOI: 10.2147/DDDT.S156467 -
Ophthalmology Aug 2005
Topics: Amides; Antihypertensive Agents; Aqueous Humor; Bimatoprost; Cloprostenol; Drinking; Glaucoma; Humans; Intraocular Pressure; Lipids; Tonometry, Ocular; Water
PubMed: 16061098
DOI: 10.1016/j.ophtha.2004.12.013 -
Expert Opinion on Pharmacotherapy Nov 2009Bimatoprost is a synthetic prostamide analog that is efficacious in the treatment of open-angle glaucoma, ocular hypertension and other forms of glaucoma. It reduces... (Review)
Review
Bimatoprost is a synthetic prostamide analog that is efficacious in the treatment of open-angle glaucoma, ocular hypertension and other forms of glaucoma. It reduces intraocular pressure (IOP) by increasing uveoscleral and trabecular outflow. When used as a 0.03% topical preparation once daily, it demonstrates sustained lowering of IOP of 7 - 8 mmHg over a 24-h period. The drug has been found to be more effective than timolol. In some studies it has shown greater ability to lower IOP when compared with other prostaglandin analogs; whereas in others all three clinically used prostaglandin analogs were found to be equally effective. It shows good IOP reduction when used in combination with other glaucoma medications. A common side effect includes mild conjunctival hyperemia, which is generally reversible. Other side effects include periorbital pigmentation, discomfort, ocular surface hyperemia and skin changes. Pharmacoeconomic data indicate that bimatoprost is cost effective in the treatment of open-angle glaucoma.
Topics: Amides; Bimatoprost; Cloprostenol; Glaucoma, Open-Angle; Humans; Intraocular Pressure
PubMed: 19874254
DOI: 10.1517/14656560903292649 -
Indian Journal of Ophthalmology Jun 2022The burden of irreversible vision loss from Glaucoma continues to rise. While the disease pathogenesis is not well understood, intraocular pressure (IOP) is the only... (Review)
Review
The burden of irreversible vision loss from Glaucoma continues to rise. While the disease pathogenesis is not well understood, intraocular pressure (IOP) is the only modifiable risk factor identified to prevent glaucomatous vision loss. Medical management remains the first-line of treatment in most adult glaucomas and the evolution of medical therapy for glaucoma has followed an exponential curve. This review tracks the rapid development of new medications and drug delivery systems in the recent years. Introduction of Rho kinase inhibitors with an entirely new mechanism of action from that of the currently used anti glaucoma medications has been a significant milestone. Latanoprostene Bunod is a novel, single molecule which provides two active metabolites that work through two different pathways for reducing intra ocular pressure. Bimatoprost implants and travoprost punctum plugs attempt to ease chronic medication use in glaucoma patients. Nanotechnology is an evolving route of drug delivery. Role of cannabinoids in medical management of glaucoma remain equivocal. The relatively short term effect on IOP, the risks of developing tolerance and side effects impacting patients' neurocognitive health greatly outweigh the potential benefit. Research on Latrunculin B, Adenosine receptor agonists, Specific gene silencing and Stem cell therapy are poised to make an impact on glaucoma treatment. While there is some evidence to support the role of Brimonidine in neuroprotection, further research is needed to clarify the role of Memantine and Neurotrophins. Evidence for benefit from dietary supplementation with Alpha lipoic acid, Forskolin , and Ginko Biloba is limited.
Topics: Antihypertensive Agents; Bimatoprost; Glaucoma; Humans; Intraocular Pressure; Tonometry, Ocular
PubMed: 35647957
DOI: 10.4103/ijo.IJO_2239_21 -
Cardiovascular Drug Reviews 2004The aim of glaucoma therapy is to preserve vision by reducing intraocular pressure (IOP). Following recent National Eye Institute sponsored studies, it is becoming... (Review)
Review
The aim of glaucoma therapy is to preserve vision by reducing intraocular pressure (IOP). Following recent National Eye Institute sponsored studies, it is becoming increasingly apparent that every mmHg of extra IOP lowering counts. Bimatoprost is the newest and most effective addition to the physician's armamentarium of ocular hypotensive drugs. Direct clinical comparisons have demonstrated that it is more efficacious than the prostaglandin (PG) FP receptor agonist prodrugs, latanoprost and travoprost, as well as a beta-adrenoceptor antagonist, timolol, alone or in fixed combination with the carbonic anhydrase inhibitor, dorzolamide. Moreover, patients that are refractory to latanoprost therapy may be successfully treated with bimatoprost. Such evidence provides support, at the clinical level, for the contention that bimatoprost is pharmacologically distinct from PG FP receptor agonist prodrugs. Bimatoprost is a structural analog of PGF2alpha-ethanolamide (prostamide F2alpha), which is formed from the endocannabinoid anandamide by a biosynthetic pathway involving cyclooxygenase-2 (COX-2). Their pharmacology is remarkably similar, such that bimatoprost may be regarded as a prostamide mimetic. The target receptor for bimatoprost and the prostamides appears unique and unrelated to PG- and endocannabinoid-sensitive receptors. Extensive ocular distribution/metabolism studies in non-human primates demonstrate that bimatoprost is not a prodrug, it remains essentially intact. Its profound ocular hypotensive effects may, therefore, be attributed to its prostamide-mimetic properties.
Topics: Amides; Animals; Antihypertensive Agents; Bimatoprost; Clinical Trials as Topic; Cloprostenol; Glaucoma; Humans; Intraocular Pressure; Lipids; Time Factors; Treatment Outcome
PubMed: 15179448
DOI: 10.1111/j.1527-3466.2004.tb00134.x -
Cardiovascular Drug Reviews 2005Bimatoprost is a safe and well-tolerated intraocular pressure (IOP) lowering drug that was approved in the United States in 2001 for the treatment of glaucoma and ocular... (Review)
Review
Bimatoprost is a safe and well-tolerated intraocular pressure (IOP) lowering drug that was approved in the United States in 2001 for the treatment of glaucoma and ocular hypertension. It is highly efficacious and produces greater mean reductions in IOP than other currently available antiglaucoma drugs. Conjunctival hyperemia is a common side effect of bimatoprost, but the hyperemia is typically mild and transient. No association has been found between signs of inflammation and the presence of hyperemia in bimatoprost-treated patients. Preclinical studies have elucidated the pharmacological mechanism of bimatoprost-related hyperemia and have examined the possible involvement of inflammation. Bimatoprost, as well as the free acid of latanoprost, elicited endothelium-dependent vasorelaxation in the rabbit jugular vein preparation, a quantitative in vitro model for ocular surface hyperemia (OSH). The vasorelaxant responses to either bimatoprost or latanoprost free acid were significantly inhibited by L-NAME, a nitric oxide synthase inhibitor. Similarly, the in vivo OSH responses to topically applied bimatoprost or latanoprost in dog eyes were significantly inhibited by L-NAME. As predicted, prostaglandin E(2) (PGE(2))-induced conjunctival hyperemia was not inhibited by L-NAME, since PGE(2) has a direct relaxant effect on the vascular smooth muscle. In-life observations and histopathological assessment of ocular surface tissues following bimatoprost treatment were performed for multiple-dose one month, 6 month, or 12 month safety studies in rabbits, dogs, and non-human primates. Results of these studies showed no evidence of bimatoprost-related inflammation in the ocular surface tissues. In summary, OSH related to bimatoprost treatment in laboratory animals occurs by endothelial-derived nitric oxide-mediated vasodilatation and is not associated with inflammation. These studies suggest that conjunctival hyperemia, a side effect of bimatoprost treatment, results from non-inflammatory, pharmacologically based vasodilatation.
Topics: Administration, Topical; Amides; Animals; Bimatoprost; Clinical Trials as Topic; Cloprostenol; Conjunctiva; Drug Evaluation, Preclinical; Enzyme Inhibitors; Humans; Hyperemia; Lipids; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase
PubMed: 16252016
DOI: 10.1111/j.1527-3466.2005.tb00168.x