FDA Rounds

Internal Medicine World Report, November 2007, Volume 0, Issue 0

Another Flu Vaccine

A new influenza vaccine, Afluria (CSL Limited), has been added to the prevention options against influenza type A and type B viruses in adults (age 18 and older). Administered as a single injection in the upper arm, the vaccine is available as a single-dose, preservative-free, prefilled syringe, or as a multidose vial with thimerosal (a mercury derivative) as a preservative. The most often reported adverse events are tenderness, pain, redness and swelling at the injection site, and headache, fatigue, and muscle aches. www.csl.com.au

New Combination Antihypertensive

A once-daily combination tablet that contains amlodipine and olmesartan medoxomil (Azor; Daiichi Sankyo) has received FDA approval as a second-line treatment of hypertension, alone or in combination with other antihypertensive agents. It will be available in 3 doses: amlodipine/olmesartan medoxomil 5/20 mg, 5/40 mg, and 10/40 mg (maximum recommended dosage). The only associated adverse event reported is edema. www.dsus.com

First Topical Osteoarthritis Gel

Diclofenac sodium topical gel (Voltaren; Novartis) 1% has been approved for the treatment of osteoarthritic joint pain in areas amenable to topical therapy, such as the knees and the hands. The gel safely delivers pain relief, with 94% less systemic absorption than comparable oral diclofenac treatment. The most common side effects are application-site reactions. www.voltarengel.com

First Integrase Inhibitor for HIV

The FDA has approved raltegravir (Isentress; Merck) tablets (400 mg) for the treatment of HIV-1 infection in combination with other antiretroviral agents. It is the first in a new class of antiretroviral agents known as integrase inhibitors, which slow the progression of the virus by blocking the integrase enzyme needed for the virus to multiply. Adverse events include diarrhea, nausea, and headache. The long-term effects of raltegravir are not yet known. www.merck.com

Injection for Complicated UTIs

Doripenem for injection (Doribax; Ortho-McNeil) has been approved as a new single-agent treatment for complicated intraabdominal and complicated urinary tract infections (UTIs), including pyelonephritis. Common adverse reactions (5% or more) include headache, nausea, diarrhea, rash, and phlebitis. www.ortho-mcneil.com

Tipranavir Now Fully Approved

Tipranavir (Aptivus; Boehringer Ingelheim), which was granted accelerated initial approval in June 2005, has been granted full (traditional) approval for treatment experienced adults infected with HIV-1 strains resistant to more than 1 protease inhibitor. Tipranavir is indicated to be coadministered with 200 mg of ritonavir (Aptivus/r). us.boehringer-ingelheim.com.

Ophthalmic Solution for Intraocular Pressure

Brimonidine tartrate/timolol maleate ophthalmic solution (Combigan; Allergan) 0.2%/0.5%, an alpha adrenergic receptor agonist with a beta adrenergic receptor inhibitor, has been approved for reducing elevated intraocular pressure in patients with glaucoma or ocular hypertension who require adjunctive or replacement therapy, because their intraocular pressure is inadequately controlled with other agents. The most common adverse reactions are allergic conjunctivitis, conjunctival folliculosis, conjunctival hyperemia, eye pruritus, and ocular burning and stinging. www.allergan.com

Expanded Coverage for Meningitis Vaccine

The approved age range for the bacterial meningitis vaccine Menactra has been expanded to include children ages 2 to 10 years. Menactra was first approved in January 2005 for people ages 11 to 55 years. Previously, Menomune was the only meningococcal vaccine available in the United States for use in children, ages 2 years or more. Both products are manufactured by Sanofi Pasteur. Both vaccines offer protection against 4 groups of Neisseria meningitidis, the bacterium that can cause meningitis.

Ixabepilone for Advanced Breast Cancer

Ixabepilone (Ixempra; Bristol-Meyers Squibb) has been approved as for the treatment of metastatic or locally advanced breast cancer that has not responded to certain other cancer drugs. The FDA evaluated ixabepilone under priority review, completing its assessment of the drug's safety and effectiveness in 6 months. Ixabepilone was approved for use in combination with another cancer drug, capecitabine (Xeloda), in patients who no longer benefit from 2 other chemotherapy treatments, including an anthracycline (eg, doxorubicin [Adriamycin RDF] or epirubicin [Epirubicin Hydrochloride]) and a taxane (eg, paclitaxel [Taxol] or docetaxel [Taxotere]). Ixabepilone was also approved for use as monotherapy in patients who no longer benefit from anthracyclines, taxanes, and capecitabine. Significant side effects associated with ixabepilone include peripheral neuropathy and bone marrow suppression. Other common adverse effects are constipation, nausea, vomiting, muscle pain, joint pain, fatigue, and general weakness. www.bms.com

Label Change for Tadalafil

Labeling changes have been approved for erectile dysfunction (ED) drugs in the class that includes tadalafil (Cialis), vardenafil (Levitra), and sildenafil (Viagra). Labeling must now more prominently display the potential risk of sudden hearing loss and guide patients on what to do if they experience sudden problems with their hearing. The FDA also plans to require the same changes in labeling for Revatio, a drug used to treat pulmonary arterial hypertension, because it contains an active ingredient used in another ED drug (sildenafil [Viagra]). The label revisions can be viewed at: www.fda.gov/cder/drug/DrugSafety/DrugIndex.htm.

New Loading Dose for Clopidogrel

The antiplatelet agent clopidogrel (Plavix; Sanofi-Aventis/Bristol-Myers Squibb) will now be available in a 300-mg tablet for use as a loading dose in acute coronary syndrome patients. www.plavix.com

Expanded Label for Sitagliptin

The FDA has expanded the use of sitagliptin (Januvia; Merck) to be used as initial therapy in combination with metformin, as add-on therapy to the sulfonylurea glimepiride (Amaryl) in patients who are not achieving adequate glycemic control with the sulfonylurea alone, and as add-on therapy to the combination of glimepiride and metformin when dual therapy does not provide adequate glycemic control. Because of postmarketing reports of hypersensitivity reactions with this agent, it is now also contraindicated in patients with a history of a serious hypersensitivity reaction to sitagliptin, including anaphylaxis and angioedema. www.merck.com

New Therapeutic Regimens

  • The HIV protease inhibitor fosamprenavir calcium (Lexiva; GlaxoSmithKline) (1400 mg) has been approved in combination with a lower dose (100 mg) of the "boosting" agent ritonavir (Norvir; Abbott), in adults who have not previously taken a protease inhibitor. www.gsk.com
  • Docetaxel injection concentrate (Taxotere; Sanofi-Aventis) has been approved in combination with cisplatin and 5-fluorouracil (Adrucil) for induction therapy of patients with locally advanced squamous cell carcinoma of the head and neck before undergoing chemoradiotherapy and surgery. www.sanofi-aventis.us

FDA Targets Unapproved Hydrocodone Products

The FDA is taking action against companies that are marketing some 2000 unapproved prescription cough-suppressant products containing hydrocodone. Hydrocodone use may impair motor skills and judgment and, in overdose, result in breathing problems or cardiac arrest. Hydrocodone formulations that have FDA approval are not affected. www.fda.gov/cder/drug/unapproved_drugs/enforcement.htm#hydrocodone

Automated Test Measures PCT in Minutes

An automated test that measures procalcitonin (PCT), a biological marker for bacterial infections, in just 20 minutes, to be used in critically ill patients to assess their risk of septic shock, has been granted marketing clearance. www.biomerieux.com/servlet/srt/bio/portail/home

Antibleeding Agent Pulled from the Market

At the FDA's request, Bayer Pharmaceuticals has agreed to suspend marketing of aprotinin (Trasylol), used to control bleeding during heart surgery, pending a detailed review of preliminary results from a Canadian study that suggested this agent was associated with an increased risk for death.

Recently, the FDA was notified that Canadian researchers had stopped a study using aprotinin because it increased mortality compared with the 2 other antifibrinolytic drugs studied. The FDA has not yet received the complete study data but expects to act quickly to undertake a thorough analysis of the data to better understand the risks and benefits of aprotinin.

Since there are few treatment options for patients at risk for excessive bleeding during cardiac surgery, the FDA is working with the manufacturer to phase aprotinin out of the marketplace in a way that does not cause shortages of other drugs used for this purpose. In 2006, the FDA revised the labeling for aprotinin to strengthen its safety warning and limit its use.