News from the World of Pharmacology
Newly Approved Drugs, New Formulations, New Indications
FDA Approves FluMist® Quadrivalent Vaccine to Prevent Seasonal Influenza
FluMist Quadrivalent becomes the first influenza vaccine to contain four strains of the influenza virus. Like the already approved FluMist (trivalent), the quadrivalent vaccine contains live-attenuated forms of the virus strains and is administered as a spray into the nose. As you know, historically, both the trivalent inactivated vaccine (TIV) and Flumist (LAIV) have used three strains of influenza virus to develop the annual vaccines, specifically, two different strains of influenza A and one strain of influenza B.
However, during a typical flu season, there may be two (or more) different strains of influenza B strains circulating. It is also possible that the one B strain selected for inclusion in the trivalent influenza vaccine may not turn out to be the influenza B strain that eventually circulates in the pending flu season. By adding a second B strain in FluMist Quadrivalent, it is hoped that the adequate protection against circulating influenza B strains. Although influenza B is generally less likely to be as dangerous or debilitating as influenza A, it does tend to have a larger impact on children, particularly young and school-aged, more than any other population.
The safety and effectiveness of FluMist Quadrivalent is supported by studies conducted previously for the FluMist trivalent formulation and three new clinical studies conducted in the United States involving about 4,000 children and adults. The studies demonstrated that the immune responses were similar between FluMist Quadrivalent and FluMist. The indications, contraindications and warnings for the guadrivalent vaccine are the same as for the current trivalent Flumist vaccine. Furthermore, adverse reactions typically reported were similar among those receiving FluMist Quadrivalent and FluMist. The most commonly reported adverse reactions were runny or stuffy nose in both children and adults, low-grade fever, headache and sore throat in adults.
New Glaucoma Drug
Zioptan™ (tafluprost ophthalmic solution) 0.0015%, the first preservative-free prostaglandin analog ophthalmic solution is approved for reducing elevated intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension. Prostaglandin analogs are often used as a first line of treatment to lower intraocular pressure in patients with open-angle glaucoma. These medicines typically lower IOP by 20% to 30%.
Tafluprost acid is a prostaglandin F2-alpha analog and, like others in this class (bimatoprost, latanoprost and travoprost), is believed to reduce intraocular pressure by increasing outflow of aqueous humor via the uveoscleral pathway.
Like bimatoprost (Latisse®), Zioptan may gradually change eyelashes and vellus hair in the treated eye. These changes include increased length, color, thickness, shape and number of lashes. Eyelash changes are usually reversible upon discontinuation of treatment. However, these products may permanently change/increase brown pigmentation of the iris, the eyelid skin, and eyelashes.
It's a go… for generic Lexapro®
Mylan® Pharmaceuticals, Inc., has launched Escitalopram Tablets USP, 5 mg, 10 mg and 20 mg, the first equivalent product to Forest Laboratories' Lexapro. Mylan was granted exclusive rights to market this product until the expiration of the pediatric exclusivity on the compound patent. However, that was short lived since the patent expired on March 14, 2012. So, in essence, Mylan had a two-week head start over other generic manufacturers.
One step closer to the "elusive" diet pill?
An Endocrinologic and Metabolic Drugs Advisory Committee recently recommended Qnexa® be granted marketing approval by the FDA for the treatment of obesity in adults. The Committee voted 20 to 2 on the recommendation for an approval based on a favorable benefit-risk profile. The original New Drug Application (NDA) was submitted in December, 2009.
Qnexa, as you might remember, is a once-a-day, oral, controlled-release formulation of low-dose phentermine and topiramate. It is believed that the combination of drugs will decrease appetite and increase satiety. In phase 2 and 3 clinical data to date, patients taking Qnexa demonstrated statistically significant weight loss (as much as 14.7% over 56 weeks). Studies also reported better glycemic control and improvement in cardiovascular risk factors when used in combination with a diet and lifestyle modification program.
The FDA is not bound by the recommendations of its advisory committees but will consider the guidance during the review of the revised New Drug Application (NDA) submitted in October 2011. The scheduled Prescription Drug User Fee Act (PDUFA) date for Qnexa is April 17, 2012. We'll see!
Alerts, Warnings and Recalls
Statins
At the end of February, the FDA issued new labeling changes for the entire statin drug class. First, based on a review of data from the JUPITER trials, the PROVE IT-TIMI 22 trials, the Women's Health Initiative (WHI) and meta-analyses, all statins (except possibly pravastatin) must now carry a warning noting that there have been reports of increased blood sugar and glycosylated hemoglobin (A1c) levels with statin use.
According to Amy G. Egan, MD, MPH, Deputy Director for Safety in the Division of Metabolism and Endocrinology Products at the FDA, the agency is not recommending that patients be discontinued from their statin therapy based on a small increase in blood sugar levels. She states that elevations in blood sugar levels should be treated with dietary and lifestyle management and/or adjustment or initiation of antidiabetic therapies. They also do not consider a slight elevation in blood sugars a reason to not continue or not initiate statins, particularly in the diabetic population where patients are at increased risk for major adverse cardiovascular events and statin therapy has been shown to reduce that risk.
Beyond the issue with elevated blood sugars, labels will now also have to include new information on the potential for cognitive side effects such as memory loss and confusion. The FDA has been unable to establish a causal relationship between these events and statin therapy and most reports are anecdotal. The reason for adding this possible side effect was to alert patients and clinicians to the fact that these reports exist, and, if patients experience persistent alteration in their thinking or cognitive functioning, they should report them to their healthcare provider.
There is no doubt that both of these new warnings will make it difficult for clinicians and patients to sort out the use of these drugs. It will take time to determine the real risk versus benefits, as well as what type of doses may be associated with risk, what subgroups and other variables. Be prepared for a lot of differing opinions in the coming months.
More straightforward in all of this is the label changes recently added to the statins regarding their use in conjunction with protease inhibitors. As you know, a number of the protease inhibitors are also inhibitors of cytochrome P450, in particular the CYP3A4 isoform which clears lovastatin, simvastatin and atorvastatin. In that regard, the FDA has notified healthcare professionals of updates to the prescribing information regarding use of HMG-CoA reductase inhibitors with protease inhibitors. Use of some of these medications together may increase the risk of myopathy or the more serious rhabdomyolysis, which can damage the kidneys and lead to kidney failure (sometimes fatal). The updates include new contraindications (lovastatin, simvastatin), warnings (atorvastatin), and maximum dose restrictions for specific HMG-CoA reductase inhibitors (atorvastatin, rosuvastatin) when combined with specific protease inhibitors used for the treatment of human immunodeficiency virus (HIV) or hepatitis C virus (HCV).
Finally, routine monitoring of liver enzymes has been removed from the drug labeling. The incidence of serious liver injury associated with the currently marketed HMG-CoA reductase inhibitors is very low and routine periodic monitoring of serum alanine aminotransferase (ALT) does not appear to detect or prevent serious liver injury, but may cause interruptions in therapy for patients with isolated increases in ALT levels, placing them at risk for cardiovascular events. Baseline liver function tests are still recommended prior to initiation of HMG-CoA Reductase Inhibitor therapy.
Are you joking with me, again?
For the second time in one month, birth control pills have been recalled by their manufacturer. This recall is not linked to the previous recall of Pfizer Lo/Ovral®-28 birth control pills. In this case, the pharmaceutical company Glenmark Generics issued a recall at the end of February for generic birth control pills containing norgestimate and ethinyl estradiol due to a packaging error. According to the recall by the India-based drug company, the oral contraceptive pills, arranged by week in four different colors to distinguish between active and inactive pills, were out of order, which can cause them to be ineffective.
Select blisters were rotated 180 degrees within the card, reversing the weekly tablet orientation and making the lot number and expiration date visible only on the outer pouch. The pills were distributed in the U.S. from September 21, 2011, through December 30, 2011. They were distributed only in the U.S.
Lot numbers affected are: 04110101, 04110106, 04110107, 04110114, 04110124, 04110129 and 04110134. The birth control pills were distributed between the months of September and December in 2011 and have expiration dates between July and September 2013.
The manufacturer stated that "consumers exposed to affected packaging should begin using a non-hormonal form of contraception immediately" and "patients who have the affected product should notify their physician and return the product to the pharmacy".
Because of the packaging error, the lot number and expiration date is visible only on the outer pouch of the product. If the lot number and expiration date cannot be read on the blister pack, the product is being recalled. For more information check here: http://www.fda.gov/Safety/Recalls/ucm293347.htm
