Drug UPDATES

Acetaminophen intravenous (IV) injection (Ofirmev) has been approved by the U.S. Food and Drug Administration (FDA) for relieving postsurgical fever and pain in patients receiving IV medications.¹ It has been studied in orthopedic patients that underwent knee or hip replacement surgery and in abdominal laparoscopic surgeries. It is approved in adults and children aged two and older.

Calcipotriene foam 0.005% (Sorilux) has been FDA approved for the topical treatment of plaque psoriasis in patients aged 18 years and older.²

Denosumab (Xgeva) has been FDA approved to prevent skeletal-related events in patients with solid tumor bone metastases (advanced cancer).³ Three late-stage clinical trials compared denosumab to zoledronic acid whereby denosumab was noninferior to the latter agent. The development of fractures was delayed for a longer period of time in denosumab-treated patients compared to zoledronic acid–treated patients with prostate or breast cancer. Zoledronic acid was superior to denosumab in delaying fracture time in patients with multiple myeloma.

Duloxetine capsules (Cymbalta) have been FDA approved to treat chronic musculoskeletal pain including chronic low back pain and osteoarthritis (OA).⁴

Immune globulin injection human 10% caprylate/chromatography purified (Gamunex-C) has been FDA approved in a subcutaneous formulation for the treatment of patients with primary immunodeficiency.⁵

Naltrexone extended-release intramuscular injection (Vivitrol) has been FDA approved as a once-monthly injection to treat and prevent relapse after patients with opioid dependence have undergone detoxification.⁶ Previously, naltrexone extended-release was approved to treat alcohol dependence. Side effects include nausea, tiredness, dizziness, headache, vomiting, decreased appetite, painful joints, and muscle cramps. Serious and severe injection site reactions have also occurred. It should only be administered by a physician using special administration needles that are provided with the product.

Pegloticase (Krystexxa) has been FDA approved for treating chronic gout in patients that are refractory to conventional treatments.⁷ A risk evaluation and mitigation strategy (REMS) is part of the product’s labeling due to the risk of severe infusion and allergic reactions. It should not be used in patients with glucose 6-phosphate dehydrogenase deficiency.

Risedronate 35 mg delayed-release tablets (Atelvia) have been FDA approved for the treatment of postmenopausal osteoporosis (PMO).⁸ They will be available in early 2011. This agent was only FDA approved to treat PMO. Dosing is once weekly immediately following breakfast with four ounces of water.⁹

Rozrolimupab (Sym001) has been granted orphan drug status for the treatment of primary immune thrombocytopenia and for Anti-RhD prophylaxis in the prevention of hemolytic disease in newborns.¹⁰ Rozrolimupab is a recombinant polyclonal antibody product. The agent is currently in phase II clinical trials.

Salzyme and selectobac dry mouth mouthwash (Orazyme) is a combination of six enzymes and other ingredients that has been FDA approved as a sugar-free rinse for the relief of xerostomia.¹¹ The formulation also is meant to inhibit gram negative bacterial growth and improve oral health to relieve general xerostomia symptoms such as oral discomfort, difficulty masticating, a rough tongue, and for the relief of mouth sores.

Sequential compression comfort sleeve (Kendall SCD) is a recently FDA-approved device that was developed to reduce venous thromboembolism risk.¹² It delivers sequential, gradient, circumferential compression mostly in nonambulatory patients and decreases patient discomfort, including sweating, heat, itchiness, pressure, and skin irritation.

Tacrolimus 5 mg capsules (generic Prograf) have garnered generic approval from the FDA.¹³

Tapentadol extended-release tablets are undergoing phase III clinical trials for the relief of pain in patients with knee OA.¹⁴ Compared to oxycodone, constipation, nausea and/or vomiting were significantly lower with tapentadol. Further studies are ongoing to more specifically delineate its adverse event profile.

Pipeline

Abatacept (Orencia) is under investigation as a subcutaneous (SC) injection and is being compared to the IV formulation.¹⁵ The newer version, given as a 150-mg dose, has performed well following an IV loading dose. Response rates were similar between both treatment groups. Injection-site reactions such as itching and erythema were more common with the SC injection, but the overall rate of injection site reactions was 1.1% and 2.5% for the SC and IV injections, respectively.

Arbaclofen placarbil (XP19986) is undergoing phase III clinical trials for the potential indication of spasticity in multiple sclerosis.¹⁶ It is a prodrug of R-baclofen and a gamma amino-butyric acid agonist.

Belimumab injection (Benlysta) was recommended for approval as a new treatment for systemic lupus erythematosus (SLE) by an FDA Advisory Panel.¹⁷ Belimumab is a monoclonal antibody that targets a protein known as the B-lymphocyte stimulator, or BLyS, which helps mediate the maturation of antibody-producing B cells. In studies, it was dosed as a 10-mg/kg injection every two weeks for the first three doses, then every four weeks thereafter. Belimumab was only slightly better than placebo in reducing lupus symptoms, but patients were also able to decrease the amount of steroids needed to control their disease.

Briakinumab, a potential new agent for treating psoriasis, has had its New Drug Application (NDA) filed with the FDA.¹⁸ It targets interleukin-12/23 and has been compared to methotrexate (MTX) and etanercept in phase III clinical trials. At 24 weeks, nearly 82% of patients using briakinumab achieved at least a 75% skin clearance rate compared with about 40% for those using MTX. Complete skin clearance was obtained in 46% of patients compared with 9% of MTX-treated patients. There were three cancers in the briakinumab-treated patients and four serious infections; there were three serious infections in the MTX-treated patients.

Buprenorphine BioErodible MucoAdhesive (BEMA) will soon be in phase III clinical trials as a treatment for moderate to severe chronic pain.¹⁹ The BEMA formulation delivers the medication through a dissolvable patch that is applied inside the cheek. If patient enrollment goes as planned, the NDA may be filed in the beginning of 2012.

Epratuzumab in combination with immunosuppressants is undergoing phase II clinical trials for the treatment of SLE. Epratuzumab is a humanized anti-CD22 monoclonal antibody.²⁰

Filgrastim injection (Neupogen) is FDA approved to treat neutropenia.²¹ Teva has applied for a generic version of this agent, and the FDA has issued a complete response letter. The letter states that no additional clinical trials are necessary, but several items were called into question. The proposed brand name is Neutroval. It has been available in the European Union since September 2008 under the brand name TevaGrastim. If approved, Amgen patents on the innovator product are set to expire in 2013.

Golimumab (Simponi) has had its NDA filed for treating patients with active psoriatic arthritis.²² Johnson & Johnson is hoping to gain approval for the indication of inhibiting the progression of structural damage and maintaining improvement in the signs and symptoms of psoriatic arthritis and improvements in physical functioning in patients with the disease.

Tasocitinib, an investigational oral JAK inhibitor, is currently undergoing phase III clinical trials as a monotherapy treatment to reduce the signs and symptoms of rheumatoid arthritis.²³ Two of three primary endpoints were met in a recent study at the end of three months of treatment.

Tiagabine hydrochloride tablets (Gabitril) have had a REMS approved to inform patients about the increased risk of suicidal behavior and thoughts associated with this class of antiepileptic agents.²⁴ The current label already contains a warning including this risk. The REMS is in the form of a medication guide.

Safety

Leflunomide tablets (Arava) have had changes to their boxed warning and warnings sections of the safety label. The changes relate to liver function test (LFT) abnormalities.²⁵ The boxed warnings and a new hepatotoxicity warning state that if alanine amino transferase (ALT) increases above three times the upper limit of normal, then leflunomide should be discontinued, and the cause of the ALT elevation should be evaluated. If the elevation is likely related to leflunomide, then use of the cholestyramine washout should be started with weekly LFT testing until the tests have normalized. If liver injury is unlikely due to the agent, than therapy can be resumed.

Finally, after years of problems associated with propoxyphene (Darvon and Darvocet), the FDA has asked that all related products, both brand and generic, be withdrawn from the U.S. market.²⁶ Recent clinical data was reported showing that propoxyphene increased the risk of potentially serious or fatal arrhythmias, which has tipped the balance toward greater risk. For long-time users of propoxyphene, it is worth noting that the arrhythmogenic potential of propoxyphene is not cumulative, and dissipates upon discontinuation of the agent if used long term. Geriatric pharmacotherapy specialists are applauding this move because it is a Beers Criteria drug, one that is potentially inappropriate for use in older adults and shows no benefit—only greatly increased—risk in this patient population. The Beers criteria were adopted by the Centers for Medicare & Medicaid Services for nursing home regulations and more recently in the development of Medicare Part D initiatives.²⁷ Propoxyphene has been well known to offer few analgesic advantages over acetaminophen while conferring significant risk, including narcotic adverse effects.

Michele Kaufman is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

References

1. Gever J. IV Acetaminophen wins approval. www.medpagetoday.com/Surgery/GeneralSurgery/23123. Published November 2, 2010. Accessed November 3, 2010.
2. FDA approves Sorilux. www.drugs.com/newdrugs/stiefel-gsk-receives-fda-approval-sorilux-calcipotriene-foam-0-005-2343.html. Published October 12, 2010. Accessed November 1, 2010.
3. Dennis M. Amgen’s Xgeva garners FDA approval to prevent cancer-related bone injury in patients with metastatic cancer. www.firstwordplus.com/Fws.do?articleid=F535427920F94A07A69857890EC03B94. Published November 19, 2010. Accessed November 22, 2010.
4. Burgess S. FDA clears Cymbalta to treat chronic musculoskeletal pain. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm232708.htm. Published November 4, 2010. Accessed November 6, 2010.
5. Talecris Biotherapeutics Receives FDA Approval for Gamunex(®)-C. www.talecris.com/press-release.htm?rel_id=1482800. Published October 14, 2010. Accessed October 20, 2010.
6. Burgess S. FDA approves injectable drug to treat opioid-dependent patients. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm229109.htm. Published October 12, 2010. Accessed October 16, 2010.
7. Riley K. FDA approves new drug for gout. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm225810.htm. Published September 14, 2010. Accessed November 17, 2010.
8. FDA approves Atelvia. www.drugs.com/newdrugs/warner-chilcott-announces-fda-approval-atelvia-next-generation-actonel-2336.html. Published October 11, 2010. Accessed November 1, 2010.
9. Gever J. Delayed-release form of Risedronate approved. www.medpagetoday.com/ProductAlert/Prescriptions/22681. Published October 11, 2010. Accessed November 18, 2010.
10. Symphogen and Swedish Orphan Biovitrum receive U.S. orphan drug designation for Rozrolimupab in ITP. www.checkorphan.org/grid/news/treatment/symphogen-and-swedish-orphan-biovitrum-receive-u-s-orphan-drug-designation-for-rozrolimupab-in-itp. Published October 6, 2010. Accessed October 16, 2010.
11. Orazyme Dry Mouth Mouthwash for xerostomia. www.empr.com/orazyme-dry-mouth-mouthwash-for-xerostomia/article/181850/. Published October 27, 2010. Accessed November 18, 2010.
12. Covidien gets an FDA clearance for comfort sleeve. www.boston.com/business/ticker/2010/11/covidien_gets_a_1.html. Published November 4, 2010. Accessed November 18, 2010.
13. Watson’s generic Prograf (R) 5 mg receives FDA approval. http://ir.watson.com/phoenix.zhtml?c=65778&p=irol-newsArticle&ID=1443895&highlight=. Published July 2, 2010. Accessed November 18, 2010.
14. Walsh N. Tapentadol eases OA pain. www.medpagetoday.com/Geriatrics/PainManagement/22053. Published September 7, 2010. Accessed November 18, 2010.
15. Gever J. ACR: Injectable abatacept as good as IV therapy. www.medpagetoday.com/MeetingCover-age/ACR/23310. Published November 12, 2010. Accessed November 18, 2010.
16. Phase 3 trial of arbaclofen placarbil (AP) for the treatment of spasticity in multiple sclerosis (MS). www.empr.com/phase-3-trial-of-arbaclofen-placarbil-ap-for-the-treatment-of-spasticity-in-multiple-sclerosis-ms/article/178807/. Published September 13, 2010. Accessed November 18, 2010.
17. Walker EP. FDA panel endorses lupus drug. www.medpagetoday.com/Rheumatology/ Lupus/23450? utm_source=breakingnews&utm_medium=email&utm_campaign=breaking-news. Published November 16, 2010. Accessed November 16, 2010.
18. Abbott psoriasis drug succeeds in pivotal trial. http://health.yahoo.net/news/s/nm/us_abbott_psoriasis. Published October 11, 2010. Accessed November 18, 2010.
19. Gallagher J. BDSI cleared to start phase III trials on new pain patch. www.bizjournals.com/triangle/news/2010/10/27/bdsi-set-to-start-phase-iii-trials-patch.html. Published October 27, 2010. Accessed November 18, 2010.
20. Epratuzumab phase IIb data presented at ACR show pipeline drug had positive effect in patients suffering from moderate to severe systemic lupus erythematosus. http://checkorphan.org/grid/news/treatment/epratuzumab-phase-iib-data-presented-at-acr-show-pipeline-drug-had-positive-effect-in-patients-suffering-from-moderate-to-severe-systemic-lupus-erythematosus. Published November 10, 2010. Accessed November 18, 2010.
21. Dane L. FDA requests further information on Teva’s proposed version of Amgen’s Neupogen. www.firstwordplus.com/Fws.do?articleid= 3B6FC3977B194597A29589C87A07D268. Published September 30, 2010. Accessed November 18, 2010.
22. Dennis M. Johnson & Johnson looks to expand US approval of Simponi in psoriatic arthritis. www.firstword plus.com/Fws.do?articleid=4CA15BC3E98146B9B9CC081A57C8CF9A. Published November 11, 2010. Accessed November 13, 2010.
23. Dane L. Pfizer’s tasocitinib meets goal of late-stage study in patients with RA. www.firstwordplus.com/Fws.do?articleid=5E35B6EFEA3D4ADA89FCAC12AD4193E5. Published November 5, 2010. Accessed November 8, 2010.
24. FDA approves REMS for Gabitril. www.empr. com/fda-approves-rems-for-gabitril/article/181037/. Published October 15, 2010. Accessed October 18, 2010.
25. Arava (leflunomide tablets) detailed view: Safety labeling changes approved by FDA Center for Drug Evaluation and Research (CDER)–September 2010. www.fda.gov/Safety/MedWatch/SafetyInformation/ucm230245.htm. Published September 2010. Accessed November 22, 2010.
26. Riley K. Xanodyne agrees to withdraw propoxyphene from the U.S. market. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm234350.htm. Published November 19, 2010. Accessed November 20, 2010.
27. Fick DM, Cooper JW, Wade WE, Waller JL, Maclean JR, Beers MH. Updating the Beers Criteria for potentially inappropriate medication use in older adults. Arch Intern Med. 2003;163:2716-2724.