Showcase, February 2014

New approval, formulations, indication, generics; hot apps; new acetaminophen warning

New approval

FDA approved influenza A (H5N1) virus monovalent vaccine, adjuvanted (ID Biomedical Corporation), for use in adults 18 years of age and older who are at increased risk of exposure to the H5N1 influenza virus, commonly known as avian or bird flu.

H5N1 has pandemic potential because it continues to infect wild birds with occasional outbreaks of influenza disease in poultry populations, and most humans have no immunity to it.

The H5N1 avian influenza vaccine is not intended for commercial availability. The U.S. Department of Health & Human Services has purchased the vaccine from the manufacturer for inclusion within the National Stockpile for distribution by public health officials if needed.

New formulations

Diclofenac (Zorvolex—Iroko Pharmaceuticals), an NSAID, is now available in 18-mg and 35-mg dosage strengths. FDA approved the drug product in October 2013 for the treatment of mild to moderate acute pain in adults. 

Diclofenac capsules contain diclofenac as submicron particles that are approximately 20 times smaller than their original size. The reduction in particle size provides an increased surface area, leading to faster dissolution. 

Most common adverse reactions in clinical trials (incidence 2%) included edema, nausea, headache, dizziness, vomiting, constipation, pruritus, flatulence, pain in extremity, and dyspepsia.

Merck announced FDA approval of raltegravir for oral suspension (Isentress), its new pediatric formulation for the treatment of HIV-1 infection. Raltegravir is now indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in patients 4 weeks of age and older who weigh 3 kg to <20 kg. 

Raltegravir inhibits the catalytic activity of HIV-1 integrase, an HIV-1 encoded enzyme that is required for viral replication. Inhibition of integrase prevents the covalent insertion, or integration, of unintegrated linear HIV-1 DNA into the host cell genome, preventing the formation of the HIV-1 provirus. 

Raltegravir for oral suspension is expected to be available during the third quarter of 2014.

New indication

FDA has granted accelerated approval for the combined use of trametinib and dabrafenib (Mekinist, Tafinlar—GlaxoSmithKline) for unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test.

The accelerated approval is contingent on the results of the ongoing Phase III Combi-D trial that is evaluating the clinical benefit of combination therapy.

Mekinist is a mitogen-activated extracellular kinase (MEK) inhibitor that blocks the activation of the protein-kinase B-raf (BRAF) pathway, thereby causing decreased cellular proliferation, cell cycle arrest, and increased apoptosis. 

Tafinlar is a selective BRAF inhibitor that blocks tumor cell growth through inhibition of some mutated forms of BRAF, including the BRAFV600 mutation.

New generics

Lupin Pharmaceuticals announced the launch of abacavir sulfate, lamivudine, and zidovudine tablets, the generic version of ViiV Healthcare’s Trizivir. The drug product is a combination of three nucleoside analogues (reverse transcriptase inhibitors) indicated for the treatment of HIV-1 infection.

The product is available in 300-mg, 150-mg, and 300-mg strengths.

Mylan and Teva received FDA approval for tolterodine tartrate extended-release (ER) capsules, the generic version of Pfizer’s Detrol LA.

Tolterodine tartrate is a muscarinic antagonist indicated for treatment of overactive bladder with symptoms of urinary frequency, urgency, or urge incontinence. 

The drug product lowers intravesicular pressure, increases capacity, and reduces the frequency of bladder contractions. It also blocks the parasympathetic nerves that control bladder voiding or exert a direct antispasmodic effect on the detrusor muscle.

Mylan’s tolterodine tartrate capsules are available in 2-mg and 4-mg dosage strengths. Teva’s tolterodine tartrate capsules are available in 2-mg and 4-mg strengths in 30-, 90-, and 500-count bottles.

Actavis received FDA approval for telmisartan immediate-release tablets, the generic version of Boehringer Ingelheim’s Micardis.

Telmisartan is a angiotension II receptor blocker that lowers blood pressure and reduces the risk of cardiovascular-related events. It is an alternative for patients who are unable to take angiotensin converting enzyme inhibitors.

Actavis’ telmisartan immediate-release tablets are available in 20-mg, 40-mg, and 80-mg dosage strengths.

Hot apps

NCI QuitPal: The National Cancer Institute’s free interactive app for iPhone or iPad offers strategies and tools to help smokers change behavior and give up smoking.

Diabetes Goal Tracker: Free American Association of Diabetes Educators app helps users manage their diabetes and set goals based on proven diabetes management approaches.

ePSS (Electronic Preventive Services Selector): Free app from U.S. Department of Health & Human Services’s Agency for Healthcare Research and Quality to help health professionals identify the screening, counseling, and preventive medication services that are appropriate for their patients. Can be searched by specific patient characteristics, such as age, sex, and selected behavioral risk factors.

Preventing Chronic Disease (PCD): Free CDC app that provides information about preventing chronic disease.

MyDS: Free app from National Institutes of Health’s Office of Dietary Supplements offering comprehensive natural medicines database; consumer version available.

ACP Immunization Advisor: Free app enables providers to search by age or underlying medical circumstance or browse the Vaccine Library to determine the vaccines their adult patients need. Contains the latest immunization news and updates from American College of Physicians.

FluView Interactive: CDC’s free app provides provides weekly influenza surveillance information in the United States.

FDA issues new warning on acetaminophen

In a January 14, 2014, alert, FDA asked all health professionals to discontinue prescribing and dispensing any products containing more than 325 mg of acetaminophen per tablet, capsule, or other dosage unit. 

FDA also recommended that when pharmacists receive a prescription for a combination product with more than 325 mg of acetaminophen per dosage unit that they the prescriber to discuss a product with a lower dose. A two-tablet or two-capsule dose may still be prescribed, if appropriate. In that case, the total dose of acetaminophen would be 650 mg (the amount in two 325-mg dosage units). 

When making individual dosing determinations, health care providers should always consider the amounts of both the acetaminophen and the opioid components in the prescription combination drug product.

The warning comes from an evaluation of medical literature that showed a greater risk of liver injury than benefit from taking doses greater than 325 mg. In January 2011, FDA asked manufacturers of prescription combination drug products containing acetaminophen to limit the amount of acetaminophen to no more than 325 mg in each tablet, capsule, or other dosage unit by January 14, 2014. 

Inadvertent overdose from prescription combination drugs containing acetaminophen accounts for nearly half of all cases of acetaminophen-related liver failure in the United States, some of which result in liver transplant or death.

Cases of severe liver injury with acetaminophen have occurred in patients who took more than the prescribed dose of an acetaminophen-containing product in a 24-hour period, took more than one acetaminophen-containing product at the same time, or drank alcohol while taking acetaminophen products.

More than half of manufacturers have voluntarily complied with FDA’s request. However, some prescription combination drug products containing more than 325 mg of acetaminophen per dosage unit remain available. In the near future, FDA intends to institute proceedings to withdraw approval of prescription combination drug products containing more than 325 mg of acetaminophen per dosage unit that remain on the market.

Acetaminophen is also widely used as an OTC pain and fever medication and is often combined with other ingredients, such as cough and cold ingredients. FDA will address OTC acetaminophen products in another regulatory action. 

Health care providers and pharmacists who have further questions are encouraged to FDA’s Division of Drug Information at 888.INFO.FDA (888-463-6332) or [email protected].