Woolley Map


April 1998 Bruce H. Woolley, Pharm.D., Editor Vol. 5, No.4


CDC has organized a Task Force of thirteen organizations that will interact daily withnational consumer, professional, and multi-cultural constituencies. The coalition willconduct a campaign to educate women of reproductive age and health care professionalsabout the need to consume folic acid to prevent the serious birth defects of spina bifidaand anencephaly. Each member organization of the Task Force will implement the campaign ina manner that will maximize their distribution resources and best educate theirconstituencies. In addition, the CDC is preparing a Folic Acid Resource Guide toprovide user-friendly technical assistance for local organizations and community healthcare providers to conduct local folic acid education campaigns that will compliment thenational effort. The Resource Guide and accompanying materials will be availableby summer 1998.


A SERM is a compound which selectively binds to and acts through the estrogenreceptor(s), but which has estrogen agonist activities in some tissues and estrogenantagonist activity in others. This classification for estrogen-like compounds wasrecently defined to describe agents which are designed to achieve the desired effects ofestrogen, such as on the skeletal and cardiovascular systems, while lacking estrogen'sstimulatory effects on the breast and uterus.

The estrogen receptor, in essence, is a transcriptional factor (site) which resides inthe nucleus of the cell. When substances bind to the estrogen receptor, that complex iscapable of activating genomic sequences to drive cellular responses to the substance.Although the molecular mechanisms of the tissue specificity of SERMs are not completelyunderstood, preliminary evidence suggests that substance-estrogen receptor complexesassociate with unique response elements, distinct from the estrogen response element,indicating that multiple transcriptional pathways may mediate the tissue-selectiveeffects. For more information see: Katzenellenbogen, Mol Endocrinol 1996;10(2):119-131; Yang, Venugopalan, Hardikar, Glasebrook, Science 1996;273(5279):1222-1225; Science 1997; 275(5304):1249.


Although most fluoroquinolones must be taken on an empty stomach, trovafloxacin tablets(

Trovan®/Pfizer) can be taken with or without food. It is recommended by thecompany that the dizziness that is experienced by 11% of patients on the 200 mg dose canbe significantly diminished if taken with food.


The FDA has granted approval of an expanded indication for dirithromycin (Dynabac®/Sanofi)for the treatment of acute bacterial exacerbations of chronic bronchitis due to Haemophilusinfluenzae and uncomplicated skin and skin structure infection due to Streptococcuspyogenes. The product is a once-daily macrolide and has an optional shorter five daycourse of therapy. Major adverse effects include gastrointestinal and abdominal pain,nausea, and diarrhea.


A study showed an increased risk of excessive blood thinning with concomitant use ofwarfarin (Coumadin®/DuPont Merck) and acetaminophen. (JAMA1998 Mar 4; 279(9): 657-62, 702-3) The authors of the study reports that "as comparedto patients who did not use acetaminophen, risk of dangerously thin blood was 10 timeshigher among those who used the equivalent of at least four regular-strength (325mg)acetaminophen tablets per day for longer than one week. Among patients who had loweracetaminophen intakes -- down to 6 or fewer regular strength tablets per week -- risk ofexcessive anticoagulation was approximately four to seven times higher."


The FDA has approved valsartan and hydrochlorothiazide (Diovan®/Novartis)for second-line treatment of hypertension. In clinical trials of greater than 1,500patients, the combination demonstrated efficacy by reducing systolic and diastolic bloodpressure greater than monotherapy. Adverse effects greater than placebo included:headache, dizziness, viral infection, fatigue, and abdominal pain.


Marketing approval has been granted by the FDA for esterified estrogens 0.3 mg tablets(Estratab® /Solvay) for the prevention of osteoporosis. In a two-yeartrial of over 400 postmenopausal women, those women receiving 0.3 mg of esterifiedestrogens experienced similar protection against bone loss as patients on higher doses ofestrogen. The patients exhibited increased bone mineral density over baseline in thespine, hip and total body. In addition, the women each received a daily supplement of1,000 mg of calcium. Side effects included: headache, nausea, breast tenderness andvaginal bleeding.


The FDA advisory panel voted 5-5 on whether to recommend orlistat (Xenical®/Roche)for marketing approval as an anti-obesity drug. The committee originally gave unanimousrecommendation for approval last May before the company withdrew the NDA to further studyits role in 11 cases of breast tumors. The medication's mechanism of action is to inhibitpancreatic lipase thus decreasing absorption of ingested lipids by about 30%.


A two-week investigational study using montelukast (Singulair®/Merck)and loratidine (Claritin®/Schering) together reduced the symptoms ofseasonal allergic rhinitis over either drug alone. Montelukast was approved last month forthe chronic treatment of asthma in adult and pediatric patients 6 years and older. Thestudy was reported at the 54th meeting of the American Academy of Allergy,Asthma, and Immunology in Washington, DC. Patients on either drug alone experienced a 16%reduction in daytime nasal symptoms. Those on both drugs experienced a 28% decrease insymptoms. The reduction on placebo was 12%.


The FDA has issued a warning to consumers about the use of the herbal dietarysupplement "Sleeping Buddha." The warning stated that the product contains theunlabeled prescription-strength benzodiazepine estazolam. The FDA notes that estazolam cancause fetal damage. The distributor, Treasure Box Products, is recalling the product.


A recent study of consecutive health food store customers showed a consumption of 5.9products per person. (Journal of the American Board of Family Practice 1997;10:265-71.) The study participants were recruited for a follow-up telephone interview attwo stores in Milwaukee suburban areas and lasted for 3 weeks. Of the 194 customers whoagreed to the interview, 136 (70.1%) completed the interview process. A total of 805supplement products was reported. Most (84.3%) considered themselves healthy but took thesupplements for prevention of potential health problems. Almost 80% based their decisionson their own investigation rather than that of a health care professional. Almost 10% wereingesting potentially toxic megadoses of vitamins A and B6.


A recent report in U.S. News & World Report that a homeopathic product calledOccillococcinum, "for the relief of colds and flu-like symptoms," is reportedlymade by incubating small amounts of a freshly killed duck's liver and heart for 40 days.The resulting substance is filtered, freeze-dried, rehydrated, diluted 1:100 repeatedly.After 200 serial dilutions, the likelihood of a single molecule of duck heart or liverremaining would be 1 in 100200. According to the report, the number 100200vastly exceeds the estimated number of molecules in the universe. The report also statedthat in 1996 it only required one duck to manufacture the product yielding total sales of$200 million.


The Tufts University Health & Nutrition Letter (November 1997) reported astudy conducted at the University of Maryland. When 9 prescription prenatal vitamintablets were tested to see whether the folate they contained would dissolve, only three ofthem met dissolution standards. "Two failed so miserably that they released less than25 percent of the folate specified on the label. That means that if swallowed by someone,more than 75 percent of the folate in those pills could possibly travel right through thebody with very little chance of being absorbed..."


St. John's Wort has been popularized as "the herbal Prozac." The herbcontains numerous active components, including hypericum. In laboratory experiments, itdoes have effects on endogenous neurotransmitters (serotonin, norepinephrine, dopamine).However, is has not been definitively demonstrated to actually cross the blood-brainbarrier (a requirement for antidepressant action).

A meta-analysis of 23 clinical trials published in the British Medical Journalfound the herb to be better than placebo after two to four weeks. The longest duration ofthe trials was 12 weeks. According to the authors of the meta-analysis, the diagnosis ofdepression was not wee established, the dosage of prescription antidepressants was low,and the dosage of a standardized extract of hypericum varied more than sixfold.

Hypericum apparently has three-fold mechanisms of action. It is reported to act as aninhibitor of serotonin reuptake, as a monoamine oxidase inhibitor, and as a significantcatechol-O-methyl transferase inhibitor. However, confirmations and consistency of thesemechanisms requires the establishment of standards of purity and potency. At present,these standards have not been established in this country. They do exist in Germany, butequating approval in Germany with effectiveness is another matter. According to Germanlaw, distributors of products licensed before 1978 are not required to documenteffectiveness claims with controlled clinical trials.

Adverse effects are reported in around 2% of those taking the substance. The majorproblem is photosensitivity which has occurred in both humans and animals.Lightheadedness, nausea and vomiting have also been reported.

The National Institutes of Health's Office of Alternative Medicine has issued a callfor proposals for investigators to evaluate the safety and effectiveness of a standardizedextract of hypericum for treating patients with major depression. It is expected that thetrials will not begin before next June with results not finalized for several years.

The Medical Letter on Drugs and Therapeutics (Nov 21, 1997) publishedan evaluation of St. John's Wort. The editors concluded: "Better, longer studies areneeded to establish the effectiveness and safety of St. John's Wort for treatment ofdepression. The active ingredients, the potency and the purity of the preparations sold inthe USA are all unknown."

The information and opinions expressed in the Therapeutics Letter do not necessarilyreflect the official policy of the sponsoring organizations.