|January 1998||Bruce H. Woolley, Pharm.D., Editor||Vol.5, No.1|
DECEMBER BUSIEST MONTH FOR DRUG APPROVALS
The month of December is usually the most productive period for theapproval of new drugs by the FDA. December of 1997 was no exception. These are the majordrug approvals:
Raloxifene (Evista®/Lilly), a selective estrogen receptormodulator, for prevention of osteoporosis in postmenopausal women.
Daclizumab (Zenapax®/Roche), the first approved human monoclonalantibody, for acute organ rejection prophylaxis in renal transplant patients.
Fomepizole (Antizol®/Orphan Medical) as a parenteral antidote forethylene glycol (antifreeze) poisoning. Fomepizole acts as an alcohol dehydrogenaseinhibitor blocking the formation of toxic ethylene glycol metabolites.
Becaplermin (Regranex®/Ortho-McNeil), a platelet-derived growthfactor gel, for the treatment of diabetic foot ulcers.
Trovafloxacin (Trovan®/Pfizer), a once-daily fluroquinolone, forthe treatment of fourteen different bacterial infections.
Repaglinide (Prandin®/Novo Nordisk), for the treatment of type 2diabetes to help manage meal-related glucose loads.
Zolmitriptan (Zomig®/Zeneca), a serotonin 1B/1D receptor agonist,for the treatment of acute migraine with or without aura in adults. The product iscontraindicated in patients with a history of MI or other significant cardiovasculardisease.
Eprosartan mesylate (Teveten®/SmithKline Beecham), an angiotensinII inhibitor, for use either alone or in combination for the treatment of hypertension.
Emedastine difumarate (Emadine®/Alcon), and antihistamineophthalmic solution for the temporary relief of allergic conjunctivitis.
Dihydroergotamine mesylate (Migranal®/Novartis), a multiplereceptor serotonin agonist nasal spray for acute relief of migraine with or without aura.
Ursodiol (URSO®/Axcan Pharma US) 250mg tablets for the treatmentof primary biliary cirrhosis. The product should not be given in conjunction with bileacid sequestering agents, aluminum containing antacids, estrogens (including oralcontraceptives), and cofibrate. It is currently available as Actigall®/Novartisfor dissolution of gallstones.
Cefdinir (Omnicef®/Warner-Lambert), a cephalosporin, for adult andpediatric treatment of community-acquired pneumonia, acute exacerbation of chronicbronchitis, acute bacterial sinusitis, pharyngitis and tonsilitis.
Somatropin [rDNA origin] (Natropin®/Genentech) for the replacementof endogenous growth hormone in patients with adult growth hormone deficiency.
Ofloxacin otic solution (Floxin®/Dalichi), a fluroquinoloneantbiotic, for the treatment of otitis externa in patients one year old and older.
Testosterone transdermal system (Testoderm TTS®/Alza) for men withtestosterone deficiency.
Finasteride (Propecia®/Merck) 1 mg for the new indication oftreating male pattern baldness. The drug must be taken indefinitely to retain the gains inamount of hair and a reduction in hair loss.
Ceftriaxone sodium (Rocephin®/Roche) as a single-dose injectionfor the treatment of acute otitis media.
Although approved last May, Toremifene citrate (Fareston®/Schering-Plough)is not available for the once-daily, first-line treatment of metastatic breast cancer inpostmenopausal women with estrogen receptor positive or receptor unknown tumors.
PRODUCTS RECOMMENDED FOR APPROVAL
Although formal approval has not yet been received, FDA advisory panels haverecommended approval for the following:
(RotaShield®/Wyeth-Lederle), a vaccine against childhoodrotavirus-induced severe gastroenteritis which causes severe diarrhea and vomiting.
(Adcon-L gel®/Gliatech) for the prevention of scar tissueformation on and around the spinal cord during lower-back surgery.
Hydroxyurea (Droxia®/Bristol-Myers Squibb) for the treatment ofmoderate to severe sickle-cell anemia in adult patients. Currently there is no approvedtreatment for the disease.
Aldesleukin (Proleukin®/Chiron) for the treatment of adultpatients with metastatic melanoma.
A "serious" safety problem with the use of four anticoagulant drugs has beenannounced by the FDA. The products are: Normiflo®/American HomeProducts, enoxaparin (Lovenox®/Rhone-Poulenc), Fragmin®/Pharmacia& Upjohn, and Orgaran®/Organon. The FDA stated that when any ofthese products are used at the same time as spinal or epidural anesthesia or spinalpuncture, bleeding or hematomas within the spinal column may occur and possibly causeparalysis.
The FDA has advised of new warning changes in the labeling of mibefradil (Posicor®/Roche)that will clarify the risk of concomitant administration with certain HMG-CoA ReductaseInhibitors (statins) which may cause potentially life-threatening statin-inducedrhabdomyolysis (a drug induced muscle injury). Mibefradil is now contraindicated inconjunction with lovastatin (Mevacor®/Merck) and simvastatin (Zocor®/Merck).Coadministration with atorvastatin (Lipitor®/Warner Lambert) orcerivastatin (Baycol®) is discouraged. An additional warning withmibefradil concerns the use of the product in patients with low heart rates.
The American Heart Association has issued a request to physicians to be cautious inprescribing sibutramine (Meridia®/Knoll). This newly approvedantiobesity drug has been reported to increase heart rate and/or elevate blood pressure insome patients. Even though two clinical trials did not show problems that were associatedwith recently withdrawn drugs in the same therapeutic category, the association wantsprescribers to monitor patients carefully.
Terfenadine (Seldane®/Hoechst-Marion Roussel) will be withdrawnfrom the market on February 1st due to the potential for fatal prolongation of the Qtcinterval. The FDA will also ban generic terfenadine products. The metabolic product ofterfenadine, fexofenadine (Allegra®/Hoechst-Marion Roussel) hasrecently been approved in combination with a decongestant.
A recent warning by the Bureau of Alcohol, Tobacco and Firearms, states that of 55ginseng products tested, 48 contained various amounts of alcohol. The tests were conductedas a result of complaints by a New York public school teacher that students were fallingasleep in class.
For the second time in a month, warnings have been issued about potential livertoxicity among patients taking troglitazone (Rezulin®/Warner-Lambert).The new warnings are linked to three deaths in Japan. The product is marketed to be usedin combination with insulin or a sulfonylurea in patients with type 2 diabetes. As ofDecember 1st, Glaxo Wellcome (who have marketing rights in Great Britain) hasvoluntarily suspended distribution in England. The FDA now recommends that liver enzymelevels be measured at the beginning of therapy, every month for the first six months,every other month for the next six months, and periodically thereafter.
BAD YEAR FOR LOWER RESPIRATORY TRACT INFECTIONS
Z-Ran, a national disease-tracking network, recently reported on an antibioticresistance study which analyzed over 15,000 isolates from 194 labs and found that 28.7% ofS. pneumoniae had a significantly decreased in vitro susceptibility inthe northeastern United States. The organization stated that community-acquired pneumoniaand acute bacterial complications of bronchitis may be more difficult to treat. They alsostated that there may a higher incidence of lower respiratory tract infections thisseason.
SEVEN DEADLY SINS OF DRUG PRESCRIBING IN THE ELDERLY
Dennis Chapron, a pharmacist, gave a presentation at the 19th ASCP MidyearConference and outlined what he referred to as the "Seven Deadly Sins of DrugPrescribing in the Elderly." They should be remembered by all health professionalsand are: 1. Failure to educate one-self regarding the potentially toxic medicationsprescribed to the elderly; 2. Failure to consider that stopping medications can provokecomplications as potentially serious as starting a new medication;
3. Failure to appreciate that even 'benign' medications can be problematic in theelderly; 4. Failure to recognize that newly released drugs can have unexpected adverseeffects in the elderly;
5. Failure to appreciate the cumulative effect of a polymedicine regimen containingdrugs with complimentary actions; 6) Failure to alter or more assiduously monitor drugtherapy during acute illness; and 7) Failure to differentiate between disease progressionand an adverse drug reaction.
DRUG SWITCHING BY PBMs
The FDA has begun investigations into the practice of "drug switching" bypharmacy benefits management companies (PBMs) that are owned or influenced by sponsors ofmedical products. The government agency has expressed concern that the practice ofreplacing one drug or device with another for financial reasons can be potentially harmfulto patients. A published draft guidance will look at the nature and extent of therelationship of a sponsor to a PBM in addition to the sponsor's control and influence.Comment by health professionals will be accepted by the agency for 90 days.
EXCIPIENTS BECOMING CONTROVERSIAL
Excipients, pharmacologically inactive ingredients present in most pharmaceuticalproducts, have recently become a politically volatile issue. Although these substances arenot physiologically active they play a significant role in the bioavailability of a drug.Although the European Union has banned the use of nearly all beef products from GreatBritain (including gelatin, tallow, glycerol, fatty acids and many surfactants) the UnitedStates has not followed suit. An investigator from the FDA stated that import restrictionsare opposed by the U.S. beef industry fearing retaliatory bans on U.S. beef products. Atthe present time there are no reported cases where bovine-based excipients have beenimplicated in human disease. However, "60 Minutes" recently reported thatcounterfeit excipients were implicated in dozens of children's deaths in Haiti in 1995 and1996. The issue will only become "hotter" and may cause questions from yourpatients.
The information and opinions expressed in the Therapeutics Letter do notnecessarily reflect the official policy of the sponsoring organizations.