OxyContin® Update The first patent of the original oxycodone (OxyContin) extended‐release formulation, which is no longer on the market, expired on April 16, 2013. The Food and Drug Administration (FDA) did not approve generics (abbreviated new drug application; ANDA) to Purdue’s original OxyContin. According to the FDA, it provides the same therapeutic benefits as Purdue’s reformulated OxyContin but has a potential increased risk of abuse; therefore, benefits do not outweigh its risks. The FDA also approved updated labeling for Purdue’s reformulated OxyContin. The new labeling states that the product has physical and chemical properties that are expected to make abuse via injection difficult and to reduce intranasal abuse. However, abuse of OxyContin by these routes, as well as the oral route, is still possible. Postmarketing assessments of the impact of reformulated OxyContin on abuse are ongoing. Actavis, formerly known as Watson, has settled a patent infringement lawsuit with Purdue related to Actavis' generic version of Purdue’s abuse‐deterrent reformulated OxyContin. If FDA approves the ANDA, Actavis will be licensed to market a defined quantity of its generic reformulated OxyContin starting January 1, 2014. However, if Actavis is unable to receive approval for its generic OxyContin ANDA prior to September 1, 2014, it will be permitted to launch a specified number of bottles of an authorized generic version of Purdue's reformulated OxyContin, starting in October 2014. Over‐the‐Counter (OTC) Levonorgestrel (Plan B One‐Step®) Teva’s levonorgestrel (Plan B One‐Step) has been approved to use without a prescription for ages 15 years and older. Approval was based on actual use studies and label‐comprehension data, showing that females 15 years and older understood that the product was not for routine use and would not prevent sexually transmitted diseases. It will be available on pharmacy shelves as OTC instead of behind the pharmacy counter. Anyone 15 years and older, including males, can purchase it with proof of age. Teva will have a security tag on the carton to prevent theft. In April 2013, a Federal judge ordered the FDA to make the emergency oral contraceptive available OTC for all ages. The FDA stated its action is not related to the recent court decision. The approval does not apply to other emergency contraceptives. American Academy of Pediatrics (AAP) Acute Otitis Media (AOM) Clinical Practice Guidelines The AAP has updated its 2004 practice guidelines on the diagnosis and management of AOM for patients six months to 12 years of age. Although fever, fussiness, and ear pain can result in a physician visit, they do not differentiate AOM from an upper respiratory infection or other minor illness. The appearance of a bulging tympanic membrane correlates with an accurate AOM diagnosis. The choice of antibiotics remains the same as in the 2004 guidelines. The guidelines continue to recommend initial antibiotic treatment in children younger than 24 months of age with a bulging tympanic membrane. However, if bulging is mild and the child does not appear ill, initial observation or watchful waiting may be used if the family is in agreement. A mechanism must be in place to ensure follow‐up and that antibiotic therapy is started if the child worsens or fails to improve within 48–72 hours of symptom onset. Amoxicillin is first‐line for most children due to its high success rate, palatability, low rate of adverse effects, and low cost. A dose of 90 mg/kg/day in two divided doses is preferred to a lower dose. Amoxicillin clavulanate at the same 90 mg/kg/day in two divided doses is the preferred second‐line choice, but should be used initially in a child with concurrent conjunctivitis or who has received amoxicillin in the previous 30 days. Ezogabine (Potiga™) Retinal Abnormalities and Skin Discoloration The FDA has issued a new warning for ezogabine (Potiga) indicated as an adjunctive treatment of partial‐onset seizures in adults. It can cause blue skin discoloration and eye abnormalities characterized by pigment changes in the retina. It is not yet known if the retinal pigment changes caused by ezogabine lead to visual impairment, although impaired visual acuity has been reported. The skin discoloration in the reported cases appeared as blue pigmentation, primarily on or around the lips or in the nail beds of the fingers or toes, but more widespread involvement of the face and legs has been observed, including scleral and conjunctival discoloration, on the white of the eyes and inside eyelids. Information on the consequences, reversibility, time to onset, and pathophysiology of the retinal and skin abnormalities is not available. The possibility of more extensive systemic involvement has not been ruled out. All patients taking ezogabine should have a baseline and periodic ophthalmologic exams that include visual acuity testing and dilated fundus photography; fluorescein angiograms, ocular coherence tomography, perimetry, and electroretinograms are also recommended. The latency of retinal abnormalities after treatment initiation is not known, although all known cases of retinal abnormalities were reported after an exposure to ezogabine of at least three years. It is not known if retinal abnormalities can begin earlier in therapy. The rate of progression of retinal abnormalities, the best method of detection of these abnormalities, and the optimal frequency of periodic ophthalmologic monitoring are also unknown. Patients who develop changes in vision or skin discoloration should contact their health care provider immediately. Blood Glucose Meters Voluntary Recalls The LifeScan unit of Johnson and Johnson initiated a recall and replacement of all OneTouch® Verio® IQ glucose meters because the meter does not provide a warning and shuts off at extremely high blood glucose levels (≥1,024 mg/dL). Abbott Diabetes Care also announced a recall and replacement of all FreeStyle InsuLinx® glucose meters because if glucose levels are extremely high (≥1,024 mg/dL), the meter will display and store in memory an incorrect test result that is exactly 1,024 mg/dL below the actual measured result. Incorrect results have the potential of leading to incorrect treatment and delaying proper treatment, which could lead to serious injury or death. Sources: www.ashp.org www.cdc.gov www.fda.gov www.medscape.com www.PTCommunity.com www.pubmed.gov Editorial Staff:
Executive Editor: Maryam Tabatabai, PharmD Deputy Editors: Donna Johnson, PharmD Carole Kerzic, RPh Raquel Holmes, RPh May 2013 Drug Information Highlights 
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The New England Journal of Medicine reports two cases of progressive multifocal leukoencephalopathy (PML) in two patients treated with oral dimethyl fumarate for psoriasis in Europe. Biogen Idec notes other compounding factors may be at play. No cases of PML have been seen with the US‐approved formulation of dimethyl fumarate (Tecfidera™), or with any of the newer oral drugs used in multiple sclerosis. Dimethyl fumarate is not FDA‐approved for psoriasis in the US. Warner Chilcott has discontinued manufacturing mesalamine (Asacol®) 400 mg delayed‐release (DR) tablets. This is based on the FDA’s guidance, recommending removal of dibutyl phalate (DBP) from all drug products. Certain phalates, used as excipients in enteric coating of certain solid oral drugs, may affect reproductive and developmental outcomes. Warner Chilcott has received approval for Delzicol™, a 400 mg DR capsule formulation of mesalamine without DBP, for the treatment of adults with mildly to moderately active ulcerative colitis (UC), and for the maintenance of remission of UC. Delzicol is bioequivalent to Asacol. A human Prothrombin Complex Concentrate (Kcentra™) from CSL Behring has received FDA approval for the urgent reversal of vitamin K antagonist (VKA, warfarin) anticoagulation in adults with acute major bleeding. Like plasma, the only other product approved for this use in the US, Kcentra is used in conjunction with vitamin K to reverse the anticoagulation effect and stop the bleeding. Unlike plasma, Kcentra does not require blood group typing or thawing, so it can be administered more quickly than frozen plasma. At recommended doses, Kcentra is used in a far lower volume than plasma. Kcentra carries a boxed warning for risk of blood clots. GlaxoSmithKline is currently experiencing a backorder for gabapentin enacarbil (Horizant®) extended‐release tablets. XenoPort will assume manufacturing and marketing of Horizant starting May 1, 2013, with the shortage expected to extend into June 2013.
Contact Information:
Maryam Tabatabai, PharmD (513) 794‐5265 www.MagellanMedicaid.com May 2013 ‐ Clinical Alert
Generic Name amlodipine and valsartan carbinoxamine maleate levonorgestrel/ ethinyl estradiol and ethinyl estradiol acyclovir ointment acitretin bromfenac doxylamine/ pyridoxine acyclovir FDA Approved New Molecular Entities (NMEs), Biologic Products (BLAs)/Orphan Drugs, and New Indications/New Formulations for Existing Products Trade Name Description Applicant no trade name The FDA approved a first time generic for Exforge®, a combination medication of a Par calcium channel blocker and an angiotensin II receptor blocker, indicated for the treatment of hypertension. As with the brand, it carries a black box warning to discontinue use if pregnancy is detected due to potential fetal harm. It is approved in 5 mg/160 mg, 10 mg/160 mg and 10 mg/320 mg tablets. The generic, 5 mg/320 mg strength, is not yet approved. Karbinal ER® Carbinoxamine maleate (Karbinal ER), a 4 mg/5 mL extended‐release oral suspension, has Tris been approved for the treatment of seasonal and perennial allergic rhinitis in patients two years of age or older and for related indications. Carbinoxamine, a histamine‐H1 receptor blocker, has anticholinergic and mild sedative properties. It is an alternative for allergy sufferers who do not respond to first and second generation antihistamines. It is dosed every 12 hours. Quartette® Levonorgestrel/ethinyl estradiol and ethinyl estradiol (Quartette) is a once‐daily 91‐day Teva extended regimen oral contraceptive indicated for the prevention of pregnancy. During the first 84 days, the dose of estrogen increases at three specific time points and the amount of progestin remains the same; this is followed by seven days of 10 mcg of ethinyl estradiol. It was designed to minimize breakthrough bleeding between menstrual periods. no trade name The FDA approved a first time generic for Zovirax® topical antiviral ointment for the Mylan management of initial genital herpes, and in limited non‐life‐threatening mucocutaneous herpes simplex virus infections in immunocompromised patients. It is approved in a 5% acyclovir 30‐gram tube. no trade name Acitretin, a first time generic for the retinoid, Soriatane®, received FDA approval to treat Barr severe psoriasis in adults. It carries the same black box warning of the branded medication to avoid use in pregnant patients or patients who intend to get pregnant up to three years after discontinuing the medication. Approved strengths are 10 mg, 17.5 mg, 22.5 mg, and 25 mg capsules administered as 25 mg to 50 mg daily. Prolensa® Prolensa, bromfenac ophthalmic solution, has been approved as a new 0.07% strength of Bausch & a nonsteroidal for the treatment of postoperative inflammation and for the reduction of Lomb ocular pain in patients undergoing cataract surgery. Patients should instill one drop in the affected eye(s) one day prior to surgery, on the day of surgery, and daily for 14 days post surgery. Bromfenac is already available as Bromday® 0.09% ophthalmic solution. Bromday is protected by new product exclusivity until October 16, 2013.
Duchesnay Diclegis® Diclegis, 10 mg doxylamine and 10 mg pyridoxine, is an antihistamine and vitamin B6 USA analog combination delayed‐release tablet indicated for the treatment of nausea and vomiting of pregnancy in women who do not respond to conservative management, which include dietary and lifestyle changes. It is the first pregnancy category A FDA‐
approved agent for this indication. It has not been studied in patients with hyperemesis gravidarum. It is dosed as two tablets orally at bedtime. It may be increased to a maximum of four tablets per day in divided doses. The need for Diclegis should be reassessed as pregnancy progresses since nausea and vomiting usually improve after the first trimester. Sitavig® The FDA has approved Sitavig, a mucoadhesive acyclovir buccal tablet, for the treatment BioAlliance
of recurrent herpes labialis (cold sores) in immunocompetent patients. A single dose of one 50 mg buccal tablet is placed under the upper gum just above the incisor tooth, on the same side as the cold sore, until gradually dissolved. It should be applied within one hour after the onset of early symptoms and before the signs of herpes labialis lesions. Alcon brimonidine/ Simbrinza® Brimonidine and brinzolamide (Simbrinza) is the only fixed combination of an alpha 2 brinzolamide adrenergic receptor agonist and a carbonic anhydrase inhibitor indicated for the reduction of intraocular pressure in patients with open‐angle glaucoma or ocular hypertension. The most common adverse events were blurred vision, eye irritation, dysgeusia, dry mouth, and eye allergy. Instill one drop in the affected eye(s) three times daily. The 10 mL bottle contains 10 mg/mL brinzolamide and 2 mg/mL brimonidine. omeprazole and no trade name A first time generic was approved by the FDA for Zegerid® oral suspension. It is a Par sodium combination of a proton pump inhibitor and an antacid to treat duodenal ulcer, bicarbonate for heartburn, and other symptoms associated with gastroesophageal reflux disease, and oral suspension erosive esophagitis. It will be available in 20 mg and 40 mg packets for oral suspension. FDA Status FDA ANDA Approval 03/28/2013 FDA NDA Approval 03/28/2013 FDA NDA Approval 03/28/2013 FDA ANDA Approval 04/03/2013 FDA ANDA Approval 04/04/2013 FDA NDA Approval 04/05/2013 FDA NDA Approval 04/08/2013 FDA NDA Approval 04/12/2013 FDA NDA Approval 04/19/2013 FDA ANDA Approval 04/19/2013 Erratum: The April 2013 Clinical Alert issue incorrectly stated the designation of Ranbaxy’s desvenlafaxine extended‐release (ER) tablets. The correct designation is that Ranbaxy’s desvenlafaxine ER tablets were approved by the NDA pathway and are not a generic to Pristiq® tablets. The ER Pristiq tablets contain the salt form desvenlafaxine succinate, whereas Ranbaxy’s product is the free base desvenlafaxine. Ranbaxy’s desvenlafaxine ER (which does not have a brand name) is bioequivalent to Pristiq but not therapeutically equivalent or substitutable. Both are approved for the treatment of major depressive disorder (MDD). The earliest possible generic for Pristiq is August 29, 2015. Page 2 www.MagellanMedicaid.com/news/ClinicalAlerts.asp