Medicolegal Issues

Market Watch


Product Withdrawal

  • Efalizumab (Raptiva), the once-weekly monoclonal antibody used to treat moderate to severe plaque psoriasis, has been withdrawn from the U.S. market due to its association with an increased risk of developing progressive multifocal leukoencephalopathy (PML).1 Four cases of PML have been confirmed, and the manufacturer has decided the risks outweigh the benefits.2

New Generics

  • Carbamazepine extended-release (generic Tegretol-XR) tablets (100 mg, 200 mg and 400 mg)3
  • Mycophenolate mofetil (generic Cellcept)4

New Drugs, Indications & Dosage Forms

  • You might have noticed some difficulty getting pancrelipase products for your patients with exocrine pancreatic insufficiency (EPI), pancreatitis, or cystic fibrosis. Here’s why: Pancreatic enzyme replacement therapies (PERT), pancreatic enzyme products (PEP), pancrelipase products, or EPI products were available prior to the formation of the U.S. Food and Drug Administration (FDA) and the Federal Food, Drug and Cosmetic Act (FDCA) of 1938.

    Until recently, none of these drug products had been marketed under approved new drug applications (NDAs). Since none of the products were subject to the NDA process, they were never subjected to safety, efficacy, bioavailability, or dose-ranging studies.5 The FDA has since decided that these agents must undergo the NDA process and, if approved, will only be available with a prescription.6

    Part of the guidance states that all approved formulations will contain “zero overfill.” In other words, the products will not have a range of lipase (90% to 165%), as they had before. Overfill leads to side effects, including diarrhea, flatulence, hyperuricosuria, hyperuricosemia, and fibrosing colonopathy.

    The new deadline to submit an NDA is April 29, 2010. The FDA has approved its first PEP agent, Creon pancrelipase, under the new guidance. It is expected to be available later this year.7

  • Amlodipine, hydrochlorothiazide (HCTZ), and valsartan (Exforge HCT) is the first—and currently only—triple-combination antihypertensive agent to receive FDA approval.8 It can be used in patients already on these three medications, or it can be used as add-on therapy in patients not adequately controlled on two agents. The manufacturer plans to price the agent the same as amlodipine/valsartan (Exforge). Dose options are amlodipine 5 mg/valsartan 160 mg/HCTZ 12.5 mg, up to a maximum of two tablets daily.9
  • Bromocriptine (Cycloset) is reformulated in a lower dose that is fast-acting and should be taken in the morning to boost dopamine levels and improve glycemic control in Type 2 diabetes patients.10 The drug is approved for monotherapy, as an adjunct to sulfonylurea therapy, or metformin plus a sulfonylurea. It’s the first diabetes agent to be FDA-approved since the guidance on cardiovascular risks. The most common side effects in clinical trials were nausea and dizziness. It should be used cautiously in patients taking antihypertensive treatment. Women who are nursing should not use it. The launch date is unknown.11
  • Golimumab (Simponi), a once-a-month tumor necrosis factor-alpha inhibitor injection, has been FDA-approved for treating moderate to severe rheumatoid arthritis, active psoriatic arthritis, and active ankylosing spondylitis.12 It carries the same warnings as other agents in the same class, including the risk of developing tuberculosis and invasive fungal infections. A risk evaluation mitigation strategy (REMS) and medication guide are required for this agent.
  • Iloperidone (Fanapt), an atypical antipsychotic, has been FDA-approved to treat adults with schizophrenia. The most common side effects in clinical trials were dizziness, dry mouth, fatigue, nasal congestion, and orthostatic hypotension. Similar to other atypical antipsychotics, iloperidone carries a boxed warning regarding increased risk of death associated with treating behavioral problems in older patients with dementia-related psychosis, as it is not FDA-approved for this use.13

New Warnings

  • Topical testosterone products (e.g., Androgel and Testim) have received a boxed warning.14 This warning is due to multiple reports of adverse effects in children exposed to the drug via contact with a topical testosterone-treated person. There are current product label precautions; however, the FDA has received reports of secondary exposure to testosterone in children 5 years old or younger. Adverse events included inappropriate genitalia enlargement, premature pubic hair development, bone age advancement, increased libido, and aggressive behavior. The FDA has provided recommendations to minimize secondary exposure. TH

Michele B. Kaufman, PharmD, BSc, RPh, is a freelance medical writer based in New York City.


  1. FDA statement on the voluntary withdrawal of Raptiva from the U.S. market. Food and Drug Administration Web site. Available at: Accessed July 2, 2009.
  2. Withdrawal of Raptiva from U.S. market. The Medical News Web site. Available at: Accessed May 12, 2009.
  3. Taro receives final FDA approval for carbamazepine extended-release tablets. Medicine News Today Web site. Available at: Accessed May 12, 2009.
  4. FDA OKs Mylan generic version of transplant drug. Forbes Web site. Available at: Accessed May 8, 2009.
  5. Exocrine Pancreatic Insufficiency Drug Products. Federal Register Web site. Available at: Accessed May 7, 2009.
  6. Guidance for industry exocrine pancreatic insufficiency drug products—submitting NDAs. FDA Web site. Available at: Accessed May 7, 2009.
  7. Phend C. FDA formally approves Creon pancrelipase. Medpage Today Web site. Available at: Accessed May 7, 2009.
  8. FDA approves Exforge HCT—the only high blood pressure treatment to combine three medications in a single pill. Novartis Web site. Available at: Accessed May 7, 2009.
  9. Phend C. FDA approves triple-drug antihypertensive polypill. Medpage Today Web site. Available at: Accessed May 7, 2009.
  10. Neergaard L. FDA backs drug that treats diabetes via the brain. Web site. Available at: Last Accessed May 8, 2009.
  11. FDA approves Cycloset. Web site. Available at: Accessed May 8, 2009.
  12. FDA approves monthly injectable drug for treating three types of immune-related arthritis. FDA Web site. Available at: Accessed April 24, 2009.
  13. FDA approves Fanapt to treat schizophrenia. FDA Web site. Available at: Accessed May 7, 2009.
  14. Testosterone gel safety concerns prompt FDA to require label changes, medication guide. FDA Web site. Available at: Accessed May 12, 2009.

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