FDA labeling system for drugs in pregnancy.

OBJECTIVE: To review the current Food and Drug Administration (FDA) pregnancy labeling system, examine the new FDA-proposed pregnancy labeling system for form and content, and provide comments on its suitability for implementation. DATA SOURCES: Data were obtained from the FDA's Web site (www.fda.gov), PubMed, Federal Register, LexisNexis, Physician's Desk Reference (PDR), Drugdex, and Current Contents. STUDY SELECTION: Research and articles involving drugs and pregnancy, drugs and lactation, and the subcommittee meeting of the FDA were included. DATA EXTRACTION: Prospective, case-control studies from pregnancy registries. DATA SYNTHESIS: Currently, only 40% of drugs in the PDR have pregnancy categories listed. The medical profession has resorted to other means to assess pregnancy risk, such as retrospective chart review, case reports, and consultation with experts such as regional drug information centers. CONCLUSIONS: The proposed pregnancy labeling system strives for more clinical usefulness by reliance on human data derived from pregnancy registries. The clinical usefulness of the new labeling remains to be seen.

Effect of common over-the-counter medications on blood alcohol levels.

OBJECTIVE: To assess the clinical and legal significance of the potential pharmacokinetic interaction between common over-the-counter (OTC) medications and alcohol that may result in increased blood alcohol levels (BALs). DATA SOURCES: A MEDLINE search (1966-February 2000) of English-language articles was performed using the terms aspirin, acetaminophen, histamine (H2)-receptor antagonist, ethanol, and blood alcohol level and then supplemented by a bibliographic review of relevant articles. STUDY SELECTION AND DATA EXTRACTION: Two H2-receptor antagonist studies using methodologies representative of other published trials and a meta-analysis of 24 H2-receptor antagonist trials were chosen for detailed review. All identified studies examining aspirin and acetaminophen were addressed. DATA SYNTHESIS: More than 30 studies have examined the potential interaction between OTC drugs and blood alcohol. Because this issue has important medical and legal implications for patients, prescribing physicians, and pharmaceutical manufacturers, a critical analysis of the literature addressing this potential interaction is presented. CONCLUSIONS: Numerous factors arguing against a clinically significant interaction were identified. First, data from the relevant studies cannot be extrapolated to the general population because of the multitude of variables that determine an individual's BAL. Also, a publication bias for small studies (< or = 10 subjects) finding a statistically significant increase in peak BAL was observed. In addition, study results supporting an increase in BAL were often irreproducible when these trials were repeated under similar conditions. Finally, although some studies detected statistically significant increases in peak BAL, these changes were often clinically irrelevant.

GHB: an important pharmacologic and clinical update.

Gamma-hydroxybutyrate (GHB) intoxication is a significant cause of morbidity and mortality in patients taking the drug for recreational purposes. Due to the recent increase in emergency room visits, hospital admissions, and deaths, it has become necessary to re-examine the pharmacology, pharmacokinetics, pharmacodynamics, clinical manifestations, and potential adverse effects associated with GHB use. We present an important pharmacologic and clinical update on GHB.

Discontinuation rates of Helicobacter pylori treatment regimens: a meta-analysis.

We conducted a meta-analysis to determine what factors in treatment regimens for Helicobacter pylori are associated with increased discontinuation rates. Studies were selected from the 1990-1996 MEDLINE data base, and references in published articles and reviews were obtained. Each article was uniformally abstracted for factors that could potentially affect dropout rates. Drug regimens with high numbers of doses per day had highest dropout rates (p=0.0001). The total dropout rate was lowest for regimens containing a proton pump inhibitor (OR = 0.75, CI 0.57, 0.98). The rate was high in regimens containing a bismuth compound due to side effects (OR = 2.79, CI 1.78, 4.36). The main finding was that drug regimens for eradication of H. pylori that have a high number of doses per day result in higher discontinuation rates than regimens with fewer doses per day.

Physicians' perceptions and knowledge of drug costs: results of a survey.

The objective of this survey was to determine physicians' opinions of the importance of drug costs, sources of drug cost information used, preferences for mechanisms to lower drug costs, and to assess knowledge of the relative cost of common drugs. A questionnaire containing opinion statements and five categories of drugs to be ranked from least to most expensive was sent to 598 physicians at our tertiary-care, university-affiliated teaching hospital. In all, 398 (66.6%) surveys were completed. Survey results indicate that physicians are interested in lowering the cost of drug therapy, and that they are knowledgeable of relative drug costs but would like more cost information to make more informed prescribing decisions. Most believe that a readily available drug cost index is the most beneficial mechanism to decrease drug expenditures.

Use of nifedipine in the hypertensive diseases of pregnancy.

OBJECTIVE: To review the available data about the use of nifedipine to treat hypertension in pregnancy. DATA SOURCES: All English language cases and studies published after 1984 and indexed in MEDLINE, Excerpta Medica, and BIOSIS PREVIEWS under the headings nifedipine, hypertension in pregnancy, uteroplacental blood flow, maternal/fetal hemodynamics, preeclampsia, and pregnancy outcome. MAIN OUTCOME MEASURES: The primary outcome indicators included the safety and antihypertensive efficacy of nifedipine in pregnancy; the effects of nifedipine on maternal/fetal hemodynamics; and the effect, if any, of nifedipine on perinatal outcome. CONCLUSIONS: Tradiational drug therapy choices for hypertension in pregnancy continue to be hydralazine for acute reduction of blood pressure and methyldopa for the management of chronic hypertension. Current data indicate that nifedipine is an appropriate second-line antihypertensive medication in pregnancy, but more clinical trials are needed before it can be considered an appropriate choice for initial therapy. As do other antihypertensive agents, nifedipine provides maternal benefit by lowering blood pressure and reducing the risk of cerebral hemorrhage and end-organ damage. However, perinatal benefit of nifedipine remains to be established.

Efficacy of nutritional supplements used by athletes.

Findings on the efficacy of nutritional supplements used by athletes are reviewed. Many athletes have turned away from anabolic steroids and toward nutritional supplements in the hope of gaining a competitive edge without threatening their health. Athletes may require slightly more protein than sedentary people do to maintain positive nitrogen balance, but it is dubious whether extra dietary protein will help someone to achieve athletic goals. Purified amino acids have become a popular if expensive form of protein supplementation; there is no scientific evidence, however, to support their use. Excessive protein supplementation can lead to dehydration, gout, liver and kidney damage, calcium loss, and gastrointestinal effects. Supplementation with vitamins and minerals in excess of recommended daily allowances appears to have no effect on muscle mass or athletic performance. Other substances touted as having ergogenic properties are carnitine, cobamamide, growth hormone releasers, octacosanol, and ginseng; again, there is no reliable scientific evidence to support claims that products containing these compounds have ergogenic potential, and heavy supplementation may lead to adverse effects. Nutritional supplements are promoted through unsubstantiated claims by magazine advertisements, health food stores, coaches, and other sources. The FDA considers nutritional supplements to be foodstuffs, not drugs, and therefore has not required that they be proved safe and effective. Dosage guidelines are inadequate, and quality control is poor. The FDA has begun to revise regulations governing labeling and health claims for these products. There is little if any evidence that nutritional supplements have ergogenic effects in athletes consuming a balanced diet, and some products have the potential for harm.

Drug-food interaction counseling programs in teaching hospitals.

The results of a survey to characterize drug-food interaction counseling programs in teaching hospitals and solicit opinions on these programs from pharmacists and dietitians are reported. A questionnaire was mailed to the pharmacy director and the director of dietary services at teaching hospitals nationwide. The questionnaire contained 33 questions relating to hospital characteristics, drug-food interaction counseling programs, and the standard calling for such programs issued by the Joint Commission on Accreditation of Healthcare Organizations. Of 792 questionnaires mailed, 425 were returned (response rate, 53.7). A majority of the pharmacists and dietitians (51.2%) did not consider their drug-food interaction counseling program to be formal; some had no program. The pharmacy department was involved more in program development than in the daily operation of such programs. The most frequent methods of identifying patients for counseling were using lists of patients' drugs and using physicians' orders. A mean of only five drugs were targeted per program. Slightly over half the respondents rated the Joint Commission standard less effective than other standards in its ability to improve patient care. A majority of teaching hospitals did not have formal drug-food interaction counseling programs. Pharmacists and dietitians did not view these programs as greatly beneficial and did not believe that the Joint Commission has clearly delineated the requirements for meeting its standard.

Patterns of prescribing isotretinoin: focus on women of childbearing potential.

OBJECTIVE: The primary objectives of this study were to determine how dermatologists currently prescribe isotretinoin and to determine if the potential for adverse effects, especially those affecting the fetus, has influenced dermatologists' prescribing patterns. DESIGN: A survey was mailed to 1618 dermatologists practicing in the US. The survey comprised 22 multiple-choice and fill-in-the-blank questions about the use of isotretinoin. Eight weeks were allowed for completion and return of the survey. SETTING: The setting of the study included dermatologists in private practice, those with academic appointments, those in administration, and a few dermatologists in other pursuits. PARTICIPANTS: The membership roster of the American Academy of Dermatology served as the sampling frame from which survey recipients were drawn. After arranging the list by zip code, a sample of dermatologists was taken by systematically choosing every fifth name on the list, giving the researchers the total sample of 1618 physicians. MAIN OUTCOME MEASURES: Questions were organized into the following sections: (1) practice status of respondent, (2) prescriber demographics, (3) influence of adverse effects on prescribing, (4) prescribing practices, (5) discontinuation of therapy, and (6) restriction of isotretinoin to dermatologists. The survey concluded by providing participants the opportunity to make further observations or comments. RESULTS: Of the 1618 surveys mailed, 670 usable responses were received (41.4 percent). Most respondents were in private practice. Data show that dermatologists were prescribing isotretinoin for indications other than those contained in the official labeling. Most physicians reported that they do perform a pregnancy test before prescribing the drug, and many require written informed consent before prescribing. Physicians report that, in general, their patients tolerate isotretinoin well. When therapy is discontinued, it is most often secondary to hypertriglyceridemia. Dermatologists believe that they should have sole authority for prescribing isotretinoin. CONCLUSIONS: Our results show that there is still a need for emphasizing the limited indications for isotretinoin and a need for effective patient education for women of childbearing potential who may be prescribed this drug.

Drugs for treatment of vulvovaginal candidiasis: comparative efficacy of agents and regimens.

Various agents are available for the treatment of vulvovaginal candidiasis. Imidazole agents (clotrimazole, miconazole, butoconazole, and terconazole) are preferred because of their greater efficacy, shorter treatment regimens, and ease of administration. Although the various imidazole compounds are equally efficacious, different treatment schedules are recommended depending on clinical situations. Additionally, different formulations are available that provide clinicians and patients with the opportunity to select the most appropriate agent.

Organization and operation of P & T Committees in the state of Florida: a survey.

To determine the structure and function of P & T Committees in Florida, a survey was initiated. Questionnaires were mailed to all 289 hospitals in the state. Topics addressed included hospital demographics (type of service provided, institution ownership, hospital size), P & T Committee structure (size of the committee, membership breakdown by specialty, chairman specialty, number of meetings per year), formulary additions (personnel authorized to request drug additions, process for adding drugs to the formulary, monitoring new drug use), and formulary systems (prevalence of therapeutic interchange programs, methods of communicating formulary changes). Overall survey response rate was 71.5%. In general, P & T Committees in Florida appear to be functioning at a relatively high level. Since there is little current information about the composition and operation of P & T Committees in hospitals around the country, it is hoped that this survey will be useful to P & T Committees that wish to upgrade or expand their activities.

Effects of cocaine on the human fetus: a review of clinical studies.

The abuse of cocaine in this country has reached epidemic proportions and has generated great concern for the effects of the drug on the fetus when used during pregnancy. Although educational campaigns cite adverse fetal effects as a deterrent to using the drug, there are limited data on which to base a true risk assessment. This paper reviews the published studies of pregnancy outcome in cocaine-abusing mothers, with special focus on structural malformations and other neonatal risks.

Therapeutic substitution in the health maintenance organization outpatient environment.

Health maintenance organizations (HMO) are growing in number as a cost-effective way of providing health care. In some, stringent formulary management policies including programs authorizing therapeutic substitution are practiced. Under this concept a drug that has been previously determined to be therapeutically equivalent to a second drug, even though it is not chemically equivalent to the prescribed drug, is automatically dispensed without contacting the prescriber. This study was undertaken to learn the extent and conditions under which therapeutic substitution is being practiced in the HMO setting. A survey was sent to all HMO in the U.S. inquiring into the operation of the pharmacy services. Specific focus was on the operation of the formulary and the policies and procedures being followed. The main goal was to learn how many programs authorize therapeutic substitution, what drugs are allowed, and what procedures are followed once the substitution is made. Of the 481 surveys sent out, 192 (40 percent) usable responses were received. Results indicate that 30.5 percent of HMO pharmacy plans allow therapeutic substitution. These programs were most likely to be of the staff-model or the group-model and least likely to be of the independent practice association type. HMO with an inhouse pharmacy more frequently had policies allowing therapeutic substitution than those using outside pharmacy services.

Generic equivalence of dermatologic products. How equivalent is equivalent?

More and more pharmaceutical products are becoming available under the generic designation as patents for their brand-name counterparts expire. Although some generic products are exact duplicates of the brand-name drug, others may vary with regard to their inactive ingredients or in other ways. Sometimes these allowable variations in product formulation are clinically significant for certain individuals. Therefore it is important for both the prescriber and the dispenser of medication to recognize potential differences in marketed products so that a truly equivalent preparation can be provided when a generic substitution is made. This article chronicles a case in which miscommunication and noncommunication led to the suboptimal treatment of a skin disease with a generic "equivalent." Suggestions are made for improving interprofessional communication so that the patient's needs are served to the maximum degree.