News from the World of Pharmacology
Newly Approved Drugs, New Formulations, New Indications
Nasal Steroids: From CFCs to Aqueous to HFAs
QNASL™ (beclomethasone dipropionate) is a new formulation of a nasally inhaled corticosteroid indicated for the treatment of seasonal and perennial allergic rhinitis in adults and adolescents 12 years of age and older. It is administered as a nonaqueous or "dry" spray delivered by an "environmentally friendly" hydrofluoroalkane (HFA) propellant (as a result of the ban on CFCs). It also offers a built-in dose counter.
Prior to the approval of QNASL, the only available options on the market for inhaled corticosteroids were aqueous formulations. Results from the manufacturer-sponsored 2010 survey entitled NASAL Allergy Survey Assessing Limitations (NASAL), showed that some nasal allergy patients reported dissatisfaction with their current allergy treatment. Healthcare providers and specialists also reported patient dissatisfaction with current nasal sprays.
A logical combo for the allergic rhinitis patient
Dymista™ Nasal Spray (azelastine hydrochloride and fluticasone proprionate) is now approved in the U.S. for the relief of symptoms of seasonal allergic rhinitis (SAR) in patients 12 years of age and older who require treatment with both an antihistamine (azelastine) and a corticosteroid (fluticasone) for symptomatic relief. The use of oral antihistamines together with nasal steroids has been a rational and commonly recommended approach to treating patients with significant symptomatology. This new drug is a logical combination that takes advantage of the fact that azelastine is an inhaled antihistamine that can be delivered together with an inhaled steroid. Furthermore, remember that azelastine not only blocks histamine H1-receptors like other antihistamine but also inhibits the release of histamine and other mediators involved in the allergic response. By itself, it can reduce hyper-reactivity of the airways, increase the motility of bronchial epithelial cilia and improve mucociliary transport. The efficacy and safety of Dymista has been documented in several studies involving over 4,000 patients, including a long-term safety study with more than 600 patients. Clinical trial results showed that Dymista provided a rapid and more complete symptomatic relief than standard treatment.The drug is administered twice daily in each nostril.
Is it Alzheimer's?
The FDA approved Amyvid™, a radioactive diagnostic agent indicated for brain imaging of beta-amyloid plaques in patients with cognitive impairment who are being evaluated for Alzheimer's Disease and other causes of cognitive decline. Amyvid binds to amyloid plaques and is detected using PET scan images of the brain. It is important to recognize that the agent is only one component in the diagnostic evaluation of patients. It is still questionable as to what the benefit(s) of the procedure will be. For example, a negative Amyvid scan only indicates little or no amyloid plaques currently present in the patient's brain which may rule out Alzheimer's Disease but not necessarily other forms of cognitive decline or dementia. Conversely, a positive Amyvid scan does not firmly establish a diagnosis of Alzheimer's Disease, or other cognitive disorder; only that there are amyloid deposits in the brain. Although such plaques are always associated with Alzheimer's Disease, they may also be present in patients with other types of neurologic conditions as well as in older people who have normal cognition. Additionally, the safety and effectiveness of Amyvid have not been established for predicting development of dementia or other neurologic condition, or monitoring responses to therapies. Besides, what do you do with a positive result? There currently aren't any medications (nor any coming sometime soon) that can halt progression, reverse or reduce the risk of developing Alzheimer's Disease!
They're still making new PDE5 inhibitors?
Fourteen years after the approval of Viagra® (sildenafil) comes the fourth PDE5 inhibitor, Stendra™ (avanafil), recently approved for the treatment of erectile dysfunction in men. It will be available in doses of 50 milligrams (mg), 100 mg or 200 mg and should be taken (as needed) about 30 minutes before sexual activity. At this time, it is not known if it offers any advantages over the PDE5 inhibitors already on the market.
Plop, plop, fizz, fizz
Binosto® (alendronate sodium) Effervescent Tablets have been approved for the treatment of osteoporosis in postmenopausal women, and as a treatment to increase bone mass in men with osteoporosis. Binosto is a once weekly, strawberry flavored effervescent tablet containing alendronate (70mg) that rapidly dissolves in 4oz of room temperature water to make a buffered solution. Based on the 70mg dose, it appears that each tablet will be a once weekly dosing option. The manufacturer claims that effervescent alendronate is formulated to offer more convenient dosing and reduced GI side effects in all patients and especially for those who do not tolerate Fosamax and other bisphosphonate tablets. This remains to be seen. It is anticipated that the drug will be commercially available, in packs of 4 and 12 tablets, in the US sometime in the third quarter of 2012.
Neupro® gets the nod for more severe disease states
A new indication has been approved for Neupro (rotigotine transdermal system). The patch is now approved for the treatment of the signs and symptoms of advanced stage idiopathic Parkinson's disease (PD) and as a treatment for moderate-to-severe primary Restless Legs Syndrome (RLS). Neupro was previously approved by the FDA for the signs and symptoms of early stage idiopathic PD. Neupro is a dopamine agonist patch that provides continuous drug delivery for patients with PD and RLS.
First pregnancy Category B basal insulin
The FDA recently approved Levemir® (insulin detemir [rDNA origin] injection) for a pregnancy Category B classification, indicating that Levemir, when used in pregnant women with diabetes, did not increase the risk of harm to the unborn baby. The label update makes Levemir the first and only basal insulin analog to have this classification. Until this decision, NPH (human insulin) was considered the standard of care for diabetes in pregnancy.
NA boost for Victoza's labeling
FDA has approved an update to the product label for Victoza® (liraglutide [rDNA origin] injection) to include data showing superior blood sugar control when compared to Januvia® (sitagliptin). Victoza also provided greater weight reduction. Both products were taken in combination with metformin in adults with type 2 diabetes. The label update was based on the FDA?s review of two large, randomized, open-label studies in adults with type 2 diabetes. Key findings from the studies include:
Patients treated with 1.2 mg and 1.8 mg of Victoza experienced greater reductions in A1C than those treated with Januvia 100 mg tablets, all in combination with metformin (-1.2% and -1.5% vs. -0.9%).
Although Victoza is not indicated for the management of obesity, weight change was observed as a secondary endpoint in those clinical trials. In that regard, Victoza provided greater weight loss versus patients treated with Januvia (5.94 and 7.26 lbs) for the 1.2 mg and 1.8 mg doses, respectively, versus 1.76 lbs for Januvia.
In a 26-week, open label study (n=665), the adverse reactions reported in =5% of the patients treated with Victoza and =5% of patients treated with Januvia were nausea (23.9% vs. 4.6%), headache (10.3% vs. 10.0%), diarrhea (9.3% vs. 4.6%) and vomiting (8.7% vs. 4.1%). Thus, although Victoza appears to show superior efficacy in glycemic control (and weight loss), it comes with a significantly greater potential for GI-related side effects.
Recently Approved Generics
- Vardenafil tablets (2.5, 5, 10, and 20 mg) have been approved as generic for Levitra®
- Vancomycin hydrochloride capsules (125 mg and 250 mg) were approved as generic for Vancocin® Capsules
- Fluvastatin sodium capsules (20 and 40 mg) are approved as generic for Lescol®
- Tinidazole tablets (250 and 500 mg) are now approved as generic for Tindamax®
Alerts, Warnings and Recalls
Drospirenone and higher risk for blood clots
The FDA has concluded that drospirenone-containing birth control pills may be associated with a higher risk for blood clots than other progestin-containing pills and has revised their labeling to reflect that some epidemiologic studies reported as high as a three-fold increase in the risk of blood clots for drospirenone-containing products when compared to products containing levonorgestrel or some other progestins, whereas other epidemiological studies found no additional risk of blood clots with drospirenone-containing products. The labels also will include a summary of the previously released results of an FDA-funded study of the blood clot risk.
RECOMMENDATION: Women should talk to their healthcare professional about their risk for blood clots before deciding which birth control method to use and healthcare professionals should consider the risks and benefits of drospirenone-containing birth control pills and a woman?s risk for developing a blood clot before prescribing these drugs.
Aliskiren-containing medications
The FDA has notified healthcare professionals of possible risks when using aliskiren or any medicines containing aliskiren together with angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with diabetes or kidney (renal) impairment. These drug combinations should not be used (are contraindicated) in patients with diabetes. In addition, avoid use of aliskiren with ARBs or ACEIs in patients with moderate to severe renal impairment (i.e., where glomerular filtration rate [GFR] < 60 mL/min). The labels for the aliskiren drugs are being updated based on preliminary data from a clinical trial, "Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)."
RECOMMENDATION: Concomitant use of aliskiren with ARBs or ACEIs in patients with diabetes is now contraindicated because of the risk of renal impairment, hypotension, and hyperkalemia. Avoid use of aliskiren with ARBs or ACEIs in patients with renal impairment where GFR < 60 mL/min.
Celexa® (citalopram) and that pesky QT interval thing
Last August, the FDA issued a Drug Safety Communication (DSC) stating that Celexa or its generic form citalopram should no longer be used at doses greater than 40 mg per day because of the potential for QT prolongation FDA has recently clarified dosing and warning recommendations as follows:
- Citalopram is not recommended for use at doses greater than 40 mg per day because such doses cause too large an effect on the QT interval and confer no additional benefit.
- Citalopram is not recommended for use in patients with congenital long QT syndrome, bradycardia, hypokalemia, or hypomagnesemia, recent acute myocardial infarction, or uncompensated heart failure.
- Citalopram use is also not recommended in patients who are taking other drugs that prolong the QT interval.
- The maximum recommended dose of citalopram is 20 mg per day for patients with hepatic impairment, patients who are older than 60 years of age, patients who are CYP 2C19 poor metabolizers, or patients who are taking concomitant cimetidine (Tagamet®) or another CYP2C19 inhibitor because these factors lead to increased blood levels of citalopram, increasing the risk of QT interval prolongation and Torsade de Pointes.
