Medicolegal Issues

End of '08 Drug Update


The FDA has approved the first nucleic acid HBV viral DNA test for measuring HBV viral load from a patient’s blood. Via HBV viral load assessment, healthcare professionals now have a highly sensitive method for gauging antiviral therapy progress in patients with chronic HBV infections.

The test is known as the COBAS TaqMan HBV Test (Roche Diagnostic Division). It is used to measure HBV levels before beginning treatment, and then follow-up levels during treatment to assess therapy response. It is estimated that approximately 1.25 million people in the U.S. are infected with HBV, with approximately 60,000 becoming infected each year. About 5,000 people die from HBV-related complications each year.8

Market watch

First-time generics:

  • Bupropion XL 300mg tablets (generic Wellbutrin XL 300mg)
  • Eplerenone tablets (generic Inspra)
  • Galantamine tablets (generic Razadyne)
  • Mycophenolate Mofetil 250- and 500-mg tablets (generic CellCept)
  • Nisoldipine ER tablets (generic Sular extended-release)
  • Pamidronate 30-, 60- and 90-mg/mL injection (generic Aredia)
  • Temazepam 7.5- and 22.5mg capsules (generic Restoril)

New Approvals

  • Clevidipine butyrate (Cleviprex, The Medicines Company) is an intravenous (IV) calcium channel blocker. It is FDA approved for treatment of hypertension in patients who cannot take oral therapy or patients for whom oral therapy does not work. It is recommended that while patients receive clevidipine infusions they undergo continuous heart rate and blood pressure monitoring until their vital signs are stable. Patients should be monitored for the prospect of rebound hypertension (HTN).1
  • Romiplostim (Nplate, Amgen) is FDA approved as the first agent to directly stimulate bone marrow to produce platelets in patients with chronic immune thrombocytopenic purpura (ITP). The FDA based its approval of romiplostim on two randomized clinical trials in patients who had at least one prior ITP treatment. The studies were six months in duration and included splenectomized and non-splenectomized patients. The FDA notes a risk evaluation and mitigation strategy has been developed to address risks associated with this agent, which will require all prescribers and patients to enroll in a special program to track the long-term safety of the drug.2
  • Tetrabenazine (Xenazine, Prestwick Pharmaceuticals) is FDA approved for the treatment of chorea in Huntington's disease (HD). Tetrabenazine is the first treatment of its kind approved in the United States for any HD symptom. The labeling contains a boxed warning regarding the appearance of serious side effects, including depression and suicidal thoughts and actions. The drug should not be used in patients who have untreated depression or who actively are suicidal. Concerns about the suicide risk are heightened in all HD patients. The medication decreases the amount of dopamine available to work at relevant brain synapses, which subsequently decreases involuntary movements. The most common side effects during clinical studies were depression, drowsiness, insomnia, nausea, and restlessness.3

New Indications and Dosage Forms

  • Nicardipine hydrochloride 20 mg (HCl, Cardene IV, EKR Therapeutics) is FDA approved in single-dose IV bags as a pre-mixed 200 mL, ready-to-use injection. The pre-mixed bags contain either dextrose or sodium chloride.4
  • Palonosetron hydrochloride (Aloxi, Eisai) is FDA approved for treating chemotherapy-induced nausea and vomiting, and is available as 0.5 mg oral capsules. It is indicated for the prevention of acute nausea and vomiting following initial and repeat courses of moderately emetogenic chemotherapy. A single dose (0.5 mg) is to be administered about one hour prior to beginning chemotherapy.5
  • Tenofovir disoproxil fumarate (Viread, Gilead) is FDA approved for treating adults with chronic hepatitis B (HBV). The approval is based on data from a pair of doubleblind clinical trials in more than 400 patients and compared tenofovir disoproxil fumarate to adefovir dipivoxil (Hepsera, Gilead). A greater percentage of patients receiving tenofovir showed a complete response to treatment, compared to patients receiving adefovir. Tenofovir is a reverse transcriptase inhibitor, already FDA approved for use in combination with other antiretroviral agents for treating HIV.6
  • Valsartan/hydrochlorothiazide tablets (Diovan HCT, Novartis) and valsartan/amlodipine tablets (Exforge, Novartis) have been FDA approved as first-line treatments of HTN in adults who are likely to need more than one drug.7

New Warnings

In October 2007, the Federal Drug and Food Administration (FDA) issued information for healthcare professionals regarding the subcutaneous use of exenatide (Byetta, Amylin Pharmaceuti-cals).9 Since then, the FDA has received at least six additional case reports of necrotizing or pancreatitis in patients taking exenatide.

Of these six cases, all patients needed hospitalization, two patients died, and four were recovering at the time of the reporting. Exenatide was discontinued in all of these patients.

If pancreatitis is suspected, exenatide and other potentially suspect drugs should be discontinued. There are no signs or symptoms distinguishing acute hemorrhagic or necrotizing pancreatitis associated with exenatide from less severe forms of pancreatitis. If pancreatitis is confirmed, appropriate treatment should be initiated and patients should be carefully monitored until they fully recover. Exenatide should not be restarted. The FDA is working with Amylin Pharmaceuticals to add stronger and more prominent warnings to the product label regarding the noted risks.

Since the last warning of natalizumab injection (Tysabri, Biogen IDEC), the FDA has informed healthcare professionals of two new cases of progressive multifocal leukoencephalopathy (PML) in European patients receiving it for more than a year as monotherapy for multiple sclerosis (MS).10

The agent currently is FDA approved to treat multiple sclerosis and Crohn’s disease. Approximately 39,000 patients have received treatment worldwide, with approximately 12,000 patients receiving treatment for at least a year. No new cases have been reported in the U.S., where approximately 7,500 patients have received the drug for more than a year and approximately 3,300 have received the drug for more than 18 months.

The FDA still believes natalizumab monotherapy may confer a lower risk of PML than usage with other immunomodulatory medications. Prescribing information for natalizumab has been revised to reflect this new information. TH

Michele B. Kaufman, PharmD, BSc, RPh, is a registered pharmacist based in New York City.


1. Peck P. IV calcium channel blocker wins FDA okay. Published August 5, 2008. Accessed October 28, 2008.

2. Riley K. FDA approves first bone marrow stimulator to treat immune-related low platelet counts. Published August 22, 2008. Accessed October 28, 2008.

4. Waknine Y. FDA approvals: stavzor, cardene IV, eovist. 579068. Published August 14, 2008. Accessed October 28, 2008.

5. Eisai Pharmaceutical Company. FDA approves ALOXI® (palonosetron HCl) capsules for prevention of acute chemotherapy-induced nausea and vomiting. release.asp? ID=147&press=195. Published August 23, 2008. Accessed October 28, 2008.

6. Monthly Prescribing Reference. www. FDA approves viread for hepatitis B. www. which/FDAApprovesVireadForHepatitisB8123/. Published August 12, 2008. Accessed October 28, 2008.

7. Nainggolan L. First ARB/CCB combo approved for initial therapy. article/ Published August 5, 2008. Accessed October 28. 2008.

8. Long P. U.S. Food & Drug Administration. FDA approves DNA test to measure hepatitis B virus levels. NEWS/2008/NEW01880.html. Published September 4, 2008. Accessed October 28, 2008.

9. U.S. Food & Drug Administration. 2007 safety alerts for human medical products—Byetta (exenatide). /safety07.htm#Byetta. Published August 18, 2008. Accessed October 28, 2008.

10. U.S. Food & Drug Administration. 2008 safety alerts for human medical products–Tysabri (natalizumab). safety/2008/safety08.htm#Tysabri2. Published August 25, 2008. Accessed October 28, 2008.

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