THERAPEUTICS REPORT
| November 1998 | Bruce H. Woolley, Pharm.D., Editor | Vol. 5, No.11 |
| Ken Hunt, Assistant Editor |
TOLCAPONE ADVISORY LETTER
An advisory letter has been sent to physicians requesting any information on liver trouble in Parkinson=s disease patients taking tolcapone (Tasmar7/Roche). The letter stated that six cases of hepatitis have been reported with two deaths. When the drug first became available in February, the company suggested that liver transaminase be monitored at inception of treatment and for six months thereafter.
REDUCING MEDICATION ERRORS
A study published in the Oct 21, 1998 edition of JAMA showed that serious medication errors in hospitals can be reduced more that 50% by implementing a computerized physician order entry (POE) system. A 15-month study of 6,711 admissions using this system showed a 55% decrease of Anonintercepted@ serious medication errors. Preventable adverse drug events (those due to error, or preventable by means currently available) declined 17%. Potential adverse drug events (errors having the potential for harm but that do not result in injury) declined 84%. The authors wrote: AThese data add to the body of knowledge suggesting that POE can reduce costs and imporve quality and suggest that hospitals should consider adopting such systems.@
BETA BLOCKERS REPORTED TO BE UNDERPRESCRIBED IN CAD
Underuse of beta-blockers in coronary artery disease (CAD) patients was reported in a national, population-based study. The authors suggested that underuse may be attributed to exaggerated concerns relative to adverse effects, especially in elderly patients, as well as nonclinical factors such as demographics, insurance requirements, and prescriber specialty. In rebuttal, they state that beta-blocker therapy is cost-effective, reduces mortality after MI, reduces ischemic events in patients with mildly symptomatic disease, and improves survival compared with diuretics when used for primary prevention in men.
Wang TJ, Stafford RD. National patterns and predictors of B-blocker use in patients with coronary artery disease. Arch Intern Med 1998 Sept; 158:1901-1906.
THE STATE OF SUPPLEMENT REGULATIONS
The Food and Drug Administration proposed a new set of regulations for allowable statements in nutritional supplements in April of this year. The regulations were delineated in response to the Dietary Supplement Health and Education Act of 1994. The proposed rules include the following:
1. No disease claims may be made.
2. Disease is identified as Aany deviation from, impairment of, or interruption of any part, organ or system (or combination thereof of the body that is manifested by a characteristic set of one or more signs or symptoms).@
3. ASigns or symptoms@ include laboratory or clinical assessments that are characteristic of a disease, such as elevated blood pressure.
4. A claim that a product helps protect against a disease (e.g., Areduces the stiffness of arthritis@) is included as a disease claim.
5. A product name that implies an effect on disease (e.g., AHepatocure@) would constitute a disease claim. General names such as ACardiohealth@ or AHealth Tabs@ would not be considered a disease claim, and would therefore be allowable.
6. Suggestions that a product helps fight a specific disease or type of diseases by stimulating the body=s defenses would be a disease claim, but general claims such as Asupports immune system@ would not.
The full text of regulations is available on the internet at http://www.verity.fda.gov/. The website also contains A common phrases and ploys@ used by fraudulent health product distributers which are not as well controlled due to restrictions put on the FDA by DSHEA.
Adapted from Nutrition Forum: New Supplement Regulations. Vol 15: August 1998
POPULAR HERBAL THERAPY FOR PROSTATE CANCER
Herbal therapies are sold as over-the-counter nutritional supplements to combat ailments ranging from depression (St. Johns Wort) to the common cold (echinacea).(1) For prostate cancer patients, an herbal combination called PC-SPES has recently emerged as a popular product to combat this condition. PC-SPES, a derivation of the Latin word for hope, is a combination of eight popular Chinese herbs which have long been used in Asia to treat various medical conditions. The herbs include chrysanthemum, isatis, licorice, lucid, ganoderma, Panax pseudoginseng, rubescens, Saw Palmetto and skullcap.
The herbs in PC-SPES have been individually reported to have estrogenic activity and kill cancer cells. Licorice, for example, competes with estradiol for the estrogen receptor.(1) Prostate cancer cells grow in the presence of testosterone. Current medical treatments are therefore aimed at blocking the production of testosterone Several recent studies have shown PC-SPES to have testosterone-lowering and estrogenic activity. H. Zhang and his team of researchers at the Cancer Institute of New Jersey reported that, in patients with prostate cancer, PC-SPES decreases both PSA and testosterone. Testosterone rose sharply after the herbs were discontinued.(2)
More recently, DiPaola, et al, reported in the New England Journal of Medicine that PC-SPES has potent estrogenic activity in ovariectomized mice. The study reported that PC-SPES lowered testosterone levels in six of six men with prostate cancer. Further, the herbal combination lowered serum levels of prostate-specific antigen in eight of eight patients in the study.(1) As it is a stimulator of estrogenic activity, PC-SPES may confound standard or experimental therapies against prostate cancer. Furthermore, many adverse effects have been reported in conjunction with PC-SPES, including allergies, nausea, fluid weight gain, impotence and blood clotting. A clinical trial sponsored by Botaniclab, a main distrubutor of PC-SPES, was halted after several patients developed blood clots.(3)
(1) DiPaola RS, Zhang H, Lambert GH, et al. Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer. NEJM, 339 (12):785-91.
(2) H. Zhang, G. Lambert, M. Gallo, S. Goodin, R. Mecker, R. Carter, M. Toledano, R.S. DiPaola. The Estrogenic Effect of The Herbal Combination PC-SPES The Cancer Institute of New Jersey/RWJMS, New Bruswick, NJ. 1998
(3) PC-SPES Has Estrogen Activity: Lowers Testosterone as Well as PSA. PSA-Rising Magazine. http://www.psa-rising.com/features/medicalpike/pcspes.htm. 1998
MORE STUDIES ON ST. JOHN=S WORT
Hypericum perforatum, the plant commonly known as St. John=s Wort is widely claimed to be an effective anti-depressant. Hypericin is a known active component in St. John=s Wort extract. However, the plant=s mechanism of action is not entirely understood, nor are all of the active constituents fully known. A study in 1997 by Muller, et al.(1), reported that hypericin=s anti-depressant action was in part due to MAO inhibition. The compound also inhibits reuptake of serotonin, NE and dopamine. Researchers further found that hyperforin is also a substantially active constituent of St. John=s Wort extract.
In addition to answering questions regarding active components of the plant and mechanism of action, the NIH Office of Alternative Medicine would like to see a long-term study on the efficacy of hypericin and the active constituents of St. John=s Wort extract. Accordingly, the Office has funded a three year, $4.3 million clinical trial to compare the effects of hypericum, a placebo and a standard antidepressant medication on patients suffering from mild to moderate depression. The patients will be followed for up to six months. No previous study on the effectiveness of hypericum have lasted longer than six weeks.(2)
(1) Muller WE, et al. Effects of hypericin extract (LI 160) in biochemical models of antidepressant activity. Pharmacopsychotherapy 1997; 30: 102-7
(2) Study information from: Nutrition Forum: Major St. John=s Wort study funded. Vol 15: August 1998
SERM DRUG TRIALS ABANDONED
Clinical trials for levormeloxifene (Novo Nordisk) have been discontinued due to adverse gynecological adverse effects such as increased possibility of developing urinary incontinence and uterovaginal prolapse. The products was under investigation as a selective estrogen receptor modulator for the treatment and management of osteoporosis.
FDA MARKETING APPROVALS
Salmeterol xinafoate inhalation powder (Serevent Diskus7/Glaxo Wellcome) for maintenance treatment of asthma in children over 4 years of age with reversible obstructive airway disease, including nocturnal symptoms.
Budesonide inhalation powder (Pulmicort Turbuhaler7/Astra) as a once-a-day inhaled corticosteroid in asthma treatment for adults and children over 6 years of age.
Midazolam (Versed Syrup7/Roche) for the treatment of anxiety in children preceding a diagnostic or therapeutic medical procedure or before the induction of general anesthesia.
Valrubicin (Valstar7/Anthra) for intravesical therapy of BCG-refractory carcinoma in situ of the urinary bladder in patients who have relapsed following standard therapy and for whom immediate cystectomy would be inadvisable due to increased morbidity or mortality.
Trastuzumab (Herceptin7/Genentech) as a single-agent treatment for patients with metastatic breast cancer whose tumors overexpress the HER2 protein and who have received one or more chemotherapy regimens.
Goserelin acetate implant (Zoladex7/Zeneca) has been granted expanded use in combination with the antiandrogen flutamide prior to and during radiation therapy for management of prostate cancer.
Levlunomide (Arava7/Hoechst Marion Roussel) for the relief of signs and symptoms of active rheumatoid arthritis in adults. The drug may also retard structural damage caused by the disease.
TELEVISION ADVERTISING OF DRUGS
A new survey reported in Health Care Business Daily indicates that consumers who contact their physician to discuss treatments seen on television increased from 19% in 1997 to 35% in 1998 even though, in general, total physician contact rates remained the same. The authors also reported that consumer awareness of prescription drugs remained approximately the same (71% in 1997 vs. 70% in 1998). However, contacts with physicians by consumers who saw DTC television increased from 8% in 1997 to 14% in 1998. Expenditures for medication advertising on DTC television increased from approximately $167.9 million in 1997 to $235.8 million in 1998.
The information and opinions expressed in the Therapeutics Letter do not necessarily reflect the official policy of the sponsoring organizations.