Ginallie E.

Tubon BSN-3C

March 26, 2013 PHARMACOLOGY

Pharmacology updates : New drugs, Alerts, Warnings & Recalls

New drugs:*Provenge*(sipuleucel-T) is the first approved "treatment vaccine" for advanced prostate cancer.*Vimovo*is a single pill fixed-dose combination of an NSAID (naproxen) and a PPI (esomeprazole). The FDA has approved the new birth control pill*Natazia*(estradiol valerate and dienogest).*Oravig(miconazole) buccal tablets have been approved for the treatment of oropharyngeal candidiasis (OPC, thrush). And there is a new formulation for*OxyContin*intended to prevent tampering and abuse. Alerts, Warnings & Recalls: *FDA wants to strengthen language regarding the risk of*Vivitrol*injection site reactions based on postmarketing reports. There has been another voluntary recall of some overthe-counter (OTC) children's and infants' liquid products manufactured in the United States, including Tylenol, Motrin, Zyrtec, and Benadryl products. Finally, the FDA has added a Boxed Warning to the label for propylthiouracil, to include information about reports

Treatment "Vaccine" For Advanced Prostate Cancer

The FDA approved a new therapy for certain men with advanced prostate cancer. Although the term vaccine usually invokes the concept of disease prevention, this new therapy, called Provenge, is actually the first vaccine approved to*treat*cancer rather than prevent cancer. In this case, it is indicated for asymptomatic or minimally symptomatic metastatic, hormone-refractory prostate cancer. Remember, in this country, prostate cancer is the second most common cancer in men, after skin cancer. Provenge (sipuleucel-T) is considered an "autologous cellular immunotherapy". It is produced by taking cells that express the antigen*Prostate Acid Phosphatase (PAP)from an individual patient's tumor and incorporating the cells into a vaccine consisting of the patient's own blood cells and a proprietary fusion protein that serves as an immune system stimulant. The immune cells are then returned to the patient in a three-dose schedule given intravenously at about two-week intervals. Provenge was tested in a randomized, double-blind, placebo-controlled, multicenter trial involving 512 CRPC patients. Patients receiving the new treatment showed an increase in overall survival of 4.1 months, with a median survival of 25.8 months compared to 21.7 for the group not receiving it. On the downside, nearly all participants had an adverse reaction of some kind, although most were mild or moderate, and included chills, fatigue, fever, back pain, headache, joint ache, and nausea. However, about 1 in 4 patients had a serious adverse reaction to Provenge, including acute infusion reactions and stroke. Of course, all this comes with a hefty price tag. A full treatment is expected to cost $93,000. The manufacturer defends that price, saying it was in line with those of other cancer drugs in terms of cost

per extra month of life provided by the drug. On the upside, the approval of this novel type of treatment is expected to spur the development of "treatment vaccines" for other cancers.

A Single Pill Combo of an NSAID and PPI

Unlike the existing Prevacid NapraPAC, which is simply an individual NSAID and a PPI blister-packed together for convenience, Vimovo is a newly approved, fixed-dose combination of delayed-release enteric-coated naproxen (NSAID) and immediate-release esomeprazole (PPI) in a single pill. It has been approved for the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, and to decrease the risk of developing gastric ulcers in patients at risk of developing NSAIDassociated gastric ulcers. Vimovo was developed as a sequential-delivery tablet formulation combining an immediate-release esomeprazole magnesium layer and an enteric-coated naproxen core. As a result, esomeprazole is released first in the stomach, prior to the dissolution of naproxen in the small intestine. The enteric coating prevents naproxen release at pH levels below 5.5, providing protection against possible local gastric toxicity of naproxen.

FDA Approves New Birth Control Pill Natazia

On the heels of a major recall of Bayer's contraceptive, Yaz, dwindling sales due to loss of patent protection, and over 1,100 pending lawsuits claiming its combination of synthetic estrogen - and particularly the progestin component drosperinone - made it more dangerous than older pills, comes a newly-approved oral contraceptive pill, Natazia (estradiol valerate and dienogest). This OC, already licensed in Europe under the brand name Qlaira, is the first four-phase oral contraceptive marketed in the United States, according to the FDA. It delivers varying doses of the hormone progestin at four times throughout each 28-day treatment cycle. Critics are having a field day. Although the manufacturer states "The safety and efficacy of Natazia as an oral contraceptive was evaluated in two multicenter phase 3 clinical trials in North America and Europe involving 1,867 women and Natazia was found to be effective as a hormonal contraceptive in both studies", there is a conspicuous absence of reported*safety*data about the new drug. Furthermore, two of the three studies that supported its approval were "non-comparative, open labeled, single arm studies" (loosely translated: not blinded and not compared to other contraceptives). A third trial was a double-blind, randomized comparative study, but it investigated the drug's effects on "bleeding pattern and cycle control", not contraception.

Buccal MIconazole
Oravig (miconazole) buccal tablets have been approved for the treatment of oropharyngeal candidiasis (OPC, thrush) in adults and children age 16 and older. Oravig utilizes an innovative buccal tablet technology that allows it to adhere to the gum for once-daily dosing that delivers miconazole directly at the local site of infection throughout the day with minimal systemic absorption. Oravig is easy-to-use and provides patients with a flavorless, odorless, and convenient treatment option that does not interfere with daily activities such as eating and drinking. As with most extended-release formulations, patients should be advised not to crush, chew, or swallow the tablet.

The FDA approval was based on two pivotal Phase III clinical trials. The first study demonstrated that Oravig completely resolved signs and symptoms of OPC at rates similar to Mycelex Troche (clotrimazole) administered five times per day in HIV-positive patients. This randomized, double-blind, double-dummy trial was conducted in 577 HIV-positive patients in 28 sites in the United States, Canada, and South Africa. A second randomized, open-label, multicenter comparative trial conducted in 282 patients who underwent radiotherapy for head and neck cancer showed that Oravig is safe and effective in this patient population who often has reduced salivary flow. Oravig, in a 50 mg dosage strength, is expected to be available in retail pharmacies in the third quarter of 2010.

New Formulation for OxyContin

The FDA approved a new formulation of OxyContin. The reformulated OxyContin is intended to prevent the drug from being cut, broken, chewed, crushed or dissolved to release more medication. The new formulation may result in less risk of overdose due to tampering and will likely result in less abuse by snorting or injection. It can, however, still be abused or misused by simply ingesting larger doses than are recommended.

Once-Daily Kaletra for Treatment-Experienced Patients

FDA approved once-daily dosing of Kaletra (lopinavir/ritonavir) for adult patients with HIV who have previously taken antiretroviral therapy. Kaletra once-daily dosing is already indicated for adult patients new to antiretroviral treatment. This approval gives treatment-experienced patients, who have HIV that responds to Kaletra, another dosing option as determined by their physician.

Alerts, Warnings and Recalls

Vivitrol
The manufacturer and the FDA notified healthcare professionals and patients of an update to the Warnings, Information for Patients, and Dosage and Administration sections of the Prescribing Information for Vivitrol, strengthening the language regarding the risk of injection site reactions based on postmarketing reports that had been received prior to June 2009. FDA requires that a Medication Guide, which communicates this and other important information about treatment, be provided to all patients. Healthcare professionals should also counsel patients about the risks and benefits of Vivitrol before an initial prescription, including those risks and benefits set forth in the new Medication Guide and Prescribing Information, and should ensure that patients understand these risks.

OTC Recall. Again!

McNeil Consumer Healthcare and FDA notified healthcare professionals of a voluntary recall of certain over-the-counter (OTC) children's and infants' liquid products manufactured in the United States, including Tylenol, Motrin, Zyrtec, and Benadryl products. Some of these products may not meet

required quality standards. This recall is not being undertaken on the basis of adverse medical events. However, as a precautionary measure, parents and caregivers should not administer these products to their children. These products were distributed in the United States and a number of other countries.

PTU
In a further action based on last year's notification of the risk of serious liver injury, including liver failure and death, with the use of propylthiouracil in adult and pediatric patients, the FDA has added a Boxed Warning to the label for propylthiouracil, to include information about reports of severe liver injury and acute liver failure, some of which have been fatal, in adult and pediatric patients using this medication. FDA has identified 32 (AERS) cases (22 adult and 10 pediatric) of serious liver injury associated with propylthiouracil use. Although both proplythiouracil and methimazole are indicated for the treatment of hyperthyroidism due to Graves' disease, healthcare professionals should carefully consider which drug to initiate in a patient recently diagnosed with Graves' disease.

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