While 2014 might not be notable for the launch of very many new pharmaceutical agents within the purview of clinic-based eye care, numerous FDA approvals have occurred this year that may be used by other providers who are caring for our patients. Though it may not be important for generalists to understand the specific prescribing details, a working knowledge of these agents will be valuable as we begin to encounter patients who have been managed with them.
The Cataract Patient
Two new drugs available for intraoperative use during cataract surgery seek to improve outcomes in the immediate postoperative period.
• ReSure Sealant (Ocular Therapeutix), which received FDA approval in January 2014, is indicated for intraoperative management of clear corneal incisions (≤3.5mm) that demonstrate leakage in adult patients. A temporarily dry ocular surface must be achievable to use this sealant.
ReSure Sealant is an in situ formed hydrogel that is mixed just before use. Its package consists of a diluent solution used to mix lyophilized polyethylene glycol (PEG) and trilysine acetate. There is a transient visualization aid (FDC Blue #1) combined with the acetate to help with placement of the hydrogel in the wound. Thus, patients allergic to this colorant (FDC Blue #1) should not be managed with ReSure Sealant.
Upon mixing, the liquid will begin to solidify via a crosslinking reaction, forming a hydrogel within 20 seconds. The hydrogel is applied to the corneal incision using a foam-tipped applicator, resulting in adherence to the ocular tissue surfaces. The sealant will remain present on the corneal incision for approximately one to three days, at which time the hydrogel will soften, detach and slough off into the tears. In a clinical trial of 304 patients who received ReSure Sealant, 31.3% of the participants still had sealant present at day three and only 2.6% had the compound present at day seven.1
The only clinical trial for which data are available was sponsored by Ocular Therapeutix. In this 488-patient study, those who underwent uncomplicated clear corneal incision cataract extraction and demonstrated wound leaks were randomized to have the wound sealed either with ReSure or with sutures. ReSure Sealant demonstrated superiority over sutures by preventing wound leaks in 95.9% of patients, compared to 65.9% of patients in the suture group. There was no significant difference in the amount of corneal edema or in the amount of surgically induced astigmatism between the two groups.1,2 This sealant has not been studied for use prophylactically on corneal incisions that do not demonstrate intraoperative leakage.
• Omidria (Omeros), approved on May 30, 2014, is another agent intended for use during cataract surgery. It is used to maintain pupil size (by inhibiting intraoperative miosis) and to reduce postoperative ocular pain. The agent is a combination of phenylephrine 1% and ketorolac 0.3% that must be diluted with ophthalmic irrigation solution; it is to used as needed during surgery. Phenylephrine acts a mydriatic agent through its α-1 adrenergic agonist activity. Ketorolac is a nonsteroidal anti-inflammatory that lowers the prostaglandin concentration, reducing pain and preventing surgically-induced miosis.
Phase III studies demonstrated that mydriasis was maintained throughout the cataract surgery in Omidria-treated subjects compared to placebo-treated eyes. After cortical clean-up, 96% of the Omidria eyes had a pupil diameter of at least 6mm while only 77% of the placebo group maintained that level of mydriasis. Pain at the 10-12 hour postoperative evaluation was significantly less in the Omidria-treated subjects compared to placebo.3 This drug is FDA pregnancy category C and should be used with caution in patients with hypertension and a history of NSAID sensitivities.
Two new systemic antibiotics have been recently approved and, while not likely to be used routinely for our patients, it is comforting to know that new agents are available for serious or life-threatening infections.
• Sivextro (tedizolid phosphate, Cubist Pharmaceuticals) is approved for the treatment of acute skin infections caused by certain susceptible bacteria, including MRSA and various Streptococcus species. Approval for this new antimicrobial was obtained on June 20, 2014. Sivextro is a prodrug that in the presence of phosphatases is converted to tedizolid. Its antimicrobial activity derives from tedizolid’s binding for the 50S subunit of bacterial ribosome, thereby inhibiting protein synthesis.
Sivextro may be administered orally or intravenously. The oral dose is 200mg daily for six days. Sivextro is approved only for patients 18 years or older and is FDA pregnancy category C.4
• Dalvance (dalbavancin, Durata Therapeutics), approved on May 23, 2014, is the newest cell wall synthesis inhibitor. It is indicated for acute bacterial skin infections caused by various strains of Staphylococcus and Streptococcus. The route of Dalvance is intravenous administration. The drug is approved for adults only and is FDA pregnancy category C.5
The FDA approved three allergen immunotherapy agents in April 2014. Each contains at a least one allergen extract:
• Ragwitek (Merck) contains pollen extract from short ragweed.6
• Grastek (Merck) contains extract from Timothy grass.7
• Oralair (Greer Labs) is a mixed allergen extract of five different pollens: Sweet Vernal, Orchard, Perennial Rye, Timothy and Kentucky Blue Grass.8
These drugs are all approved for the treatment of pollen-induced allergic rhinitis with or without conjunctivitis, as confirmed by a positive skin test or in vitro testing for pollen-specific IgE antibodies for the allergen extract being used.
The exact mechanism of allergen immunotherapy is not known. Ragwitek, Grastek and Oralair are all sublingual tablets to be used in adults. The first dose should be administered in-office by a practitioner experienced in management of local allergic reactions. The patient should be observed closely for 30 to 45 minutes to rule out a severe allergic reaction. If tolerated, the patient then self-administers one tablet daily. Treatment should begin at least three months before the expected onset of the particular pollen season and continued throughout. In clinical trials, all three agents reduced nasal and ocular symptoms compared to placebo.6-8
Afrezza (MannKind Corporation) was approved on June 27, 2014 as a novel route of delivering short-acting insulin. Afrezza is inhaled insulin to be used at the beginning of each meal or within 20 minutes of beginning a meal. Peak insulin levels occur within 12 to 15 minutes of inhalation and decline to baseline after approximately three hours. Afrezza is to be used in conjunction with long-acting insulin. It is contraindicated during periods of hypoglycemia, insulin hypersensitivity and in patients with chronic lung disease. It is estimated that approximately 8.3% of the US population has diabetes and this new, convenient route of regulating glycemic control is high impact.9,10 Tables are available to convert traditional injectable insulin doses to Afrezza, which is available in four- and eight-unit single-use cartridges for oral inhalation.
Hetlioz (tasimelteon, Vanda Pharmaceuticals), approved earlier this year, is the only FDA-approved drug indicated for the treatment of non-24-hour sleep-wake disorder, a chronic disruption of a person’s circadian rhythms that is thought to affect up to 70% of patients who are totally blind.11
Hetlioz is a melatonin receptor agonist. These melatonin receptors are thought to be involved in the control of circadian rhythms. Hetlioz is dosed 20mg daily before bedtime. Efficacy and safety in pediatric patients has not been studied. It is FDA pregnancy category C.12
1.www.fda.gov/medicaldevices/productsandmedicalprocedures/deviceapprovalsandclearances/recently-approveddevices/ucm381099.htm accessed 8/1/2014.
2. Kim T, Levenson J, Tyson, F. Randomized Controlled Study of an Ocular Sealant to Prevent Wound Leak After Cataract Surgery. Poster presented at: American Academy of Ophthalmology Annual Meeting. 2013 Nov 16-19; New Orleans, LA.
3. www.accessdata.fda.gov/drugsatfda_docs/label/2014/205388s000lbl.pdf accessed 7/30/2014.
4. www.accessdata.fda.gov/drugsatfda_docs/label/2014/205435s000lbl.pdf accessed 8/1/2014.
5. www.accessdata.fda.gov/drugsatfda_docs/label/2014/021883s000lbl.pdf accessed 8/1/2014.
6. www.fda.gov/downloads/BiologicsBloodVaccines/Allergenics/UCM393600.pdf accessed 8/1/2014.
7. www.fda.gov/downloads/BiologicsBloodVaccines/Allergenics/UCM393184.pdf accessed 7/30/2014.
8. www.fda.gov/downloads/BiologicsBloodVaccines/Allergenics/UCM391580.pdf accessed 8/1/2014.
9. www.accessdata.fda.gov/drugsatfda_docs/label/2014/022472lbl.pdf accessed 7/30/2014.
10. Traynor K. Inhaled insulin product approved. Am J Health Syst Pharm. 2014 Aug 1;71(5):1238.
11. Dhillon S, Clarke M. Tasimelteon: first global pproval. Drugs. 2014 Mar;74(4):505-11.
12. www.accessdata.fda.gov/drugsatfda_docs/label/2014/205677s000lbledt.pdf accessed 8/1/2014.