Levonorgestrel subdermal implants. Contraception on trial.

When they were introduced to the world market in the 1980s, levonorgestrel subdermal implants offered the promise of an exciting alternative to traditional hormonal contraception. They provide highly effective, long-acting protection from pregnancy, without the need for user compliance. Broad acceptability of the drug has been reported throughout the world. Recently, however, the implants have met with opposition. The drug is associated with a variety of adverse effects, and removal of implants can be problematic. Serious events have been reported in women using levonorgestrel subdermal implants, although causal relationships have not been demonstrated. Additionally, concerns have been raised over the potential for coercive use of the drug. Numerous law suits have been filed alleging serious problems with implants. As a result, the drug has received considerable negative media attention. Before the controversy over levonorgestrel subdermal implants erupted, contraceptive development had declined, resulting from limitations to profits and funding, legal threats, and changes in the insurance industry. The levonorgestrel subdermal implant experience may serve to accelerate this trend. While the introduction of levonorgestrel subdermal implants offered an alternative to the current array of medical contraception, its experience may serve to dampen future contraceptive development efforts. Costly litigation and much controversy involving the implants have acted to create disincentives to further research and development of new methods of medical contraception.

IOC rescinds ban on birth control drug.

PIP: The controversy over the International Olympic Committee (IOC) ban on norethindrone, a progestin found in most oral contraceptives (OCs), and the subsequent rescinding of this ban illustrate problems inherent in the drug testing process. The ban was overturned in September 1987, after being in effect for 5 months, largely as a result of pressure from major sports organizations. The initial ban was imposed because some drug testing laboratories have trouble differentiating the metabolites of norethindrone and nandrolone, a common anabolic-androgenic steroid. Although the ostensible reason for the ban was to prevent confusion over false-positive results, the IOC also feared that some athletes who use nandrolone would begin using norethindrone to conceal their steroid use. Enforcement of the ban would have required about 80% of female athletes who rely on OCs to change brands. Although 9 of the 31 OC brands available do not contain norethindrone, norethindrone is associated with reduced side effects. Some athletes would have turned to less effective methods of birth control, making the ban an attack on the reproductive well-being of this group of women. Another concern was that the ban would have dictated prescription guidelines to physicians, even though norethindrone has a legitimate medical purpose and is not a performance-enhancing drug. Overall, sports officials argued that the ban greatly damaged the credibility of drug testing programs. It has subsequently been shown that norethindrone and nandrolone are easily distinguishable with careful analysis of drug testing results.^ieng

Medical groups and health care providers petition FDA to relabel six oral contraceptives as "morning after pills".

PIP: In the US, the American Public Health Association, the American Medical Women's Association, and Planned Parenthood of New York City have filed a citizen's petition with the Food and Drug Administration urging that 6 oral contraceptives (OCs) currently available be relabeled to include information about their use as emergency postcoital contraceptives. These drugs have been proven safe and effective in preventing pregnancy when used postcoitally, yet current labeling withholds information about this use from physicians and women in apparent violation of regulatory requirements for OCs which mandate information on all approved uses. The 6 brands involved are Ovral, Lo/Ovral, Nordette, Triphasil, Levlen, and Tri-Levlen. Postcoital contraception reduces the risk of pregnancy by 75% and acts prior to implantation (and thus does not terminate a pregnancy). Relabeling the 6 brands of OCs could decrease the number of unintended pregnancies in the US by 1.7-2.3 million annually and may obviate the occurrence of as many as a million abortions each year.^ieng

Estrogens + patient package insert = confused patients.

A brief review of the patient package inserts concept and estrogen pharmacology is presented. Then the need for patient education is discussed along with recommendations for a team approach to managing patient anxiety by helping patients understand the estrogen-containing products they are using.

PIP: This article takes issue with the physicians' handling of patient inserts in estrogen-containing medications when presenting such medication to a patient in need. This discussion follows a brief review of the rationale of the Food and Drug Administration of using package inserts and a review of estrogen uses, adverse reactions, cautions, and side effects. The author argues for a more cooperative approach to patient package inserts, which would require direct participation by the physician rather than simple passive reading by the patient. A questionnaire survey on patients' attitudes, knowledge, views, and sources of drug information on oral contraceptives, with particular attention to the role of the patient-oriented package insert, concluded that professional sources (physician, nurse, or pharmacist) were preferred over nonprofessional and media sources. A collaborative approach to drug education is recommended, and suggestions for implementation are set forth.

[Ovulation inhibitors in under age persons]. / Ovulationshemmer für Minderjährige.

PIP: The legal aspects of prescribing ovulation inhibitors to minors is discussed. Each doctor must decide for himself if he will prescribe such medications to minors. They should not be prescribed to girls under 16, who generally have not stopped growing and have irregular menstrual periods. The decision to prescribe ovulation inhibitors to girls 16-18 years of age depends on the girl's maturity and legal status. In most cases the parent or legal guardian should give his approval. A minor can legally receive ovulation inhibitors without parental consent if she is regularly independently employed and the purpose is to restore her capability to work, or if she is independently employed and insured. If the girl has a right to obtain ovulation inhibitors without parental consent, it is also her sole decision if anyone is to be informed of the prescription or examination.^ieng

Phillips v. G.D. Searle and Co., 12 September 1989.

PIP: In 1989, a US Court of Appeals ruled in cases relating to IUD injuries that if a claimant had a personal belief or had received a professional opinion that an IUD was causing injury more than three years before they filed for damages, the case was time barred by a Maryland three-year statute of limitations. Also during 1989, other US court rulings concerning the IUD concluded that 1) an action for injuries accrues from the time the device was removed and an action for breach of warranty accrues at the time the device was inserted, 2) actions are not barred by the statute of limitation, 3) a one-year statute of limitations begins running at the time the patient was hospitalized with pelvic infection, 4) an award of $7 million in punitive damages is not excessive, 5) the statute of limitations begins running from the time of the last medical treatment, and 6) the statute of limitations begins to run at the time of the last treatment. With respect to other contraceptives, 1989 court decisions allowed a settlement in a proposed class action suit against the manufacturer of the Dalkon Shield and disallowed a claim that a plaintiff should have been directly warned about the danger of stroke associated with the use of oral contraceptives.^ieng

Mexico approves Norplant.

PIP: In 1991, Mexico became the 20th country to approve the use of Norplant, the subdermal contraceptive implant. Marketing of the drug was endorsed by the Ministry of Health following an evaluation of the experiences of more than 1200 women volunteers during clinical trials at 12 clinics throughout the country.^ieng

Overview of Norplant litigation.

PIP: Norplant is a long-acting subdermal contraceptive implant system introduced to the US market in February 1991. More than one million women in the US and more than 2.5 million women internationally use Norplant. Within two years of Norplant's arrival on the US market, litigation was filed, mainly against the Norplant manufacturer, Wyeth-Ayerst Laboratories, by women who have suffered or who will suffer permanent injuries as a result of the system. Some medical malpractice claims are being filed against health care providers who prescribe and/or remove the system. Current litigation questions the safety of Norplant, the adequacy of warnings about side effects and potential adverse reactions, the degree of disclosure for informed consent, and the adequacy of training involving the product. Nurse practitioners involved with Norplant need to be aware of related litigation in order to provide the highest quality health care and avoid exposure to liability. In particular, nurse practitioners who have been trained in the insertion and removal of Norplant must be sure that they have the requisite skills and experience to respond to the known complications of the system. The author offers an overview of litigation against Norplant.^ieng

Another "excuse" puts pill licensing on hold. Women in Japan.

PIP: On March 2, 1998, Japan's Ministry of Health announced postponement of its licensing of the low-dose oral contraceptive (OC) until further studies can determine whether OC use is linked to the spread of endocrine-disrupting chemicals in the environment (secreted in the urine and feces of users). The Ministry also called for research into the relationship of the OC and cervical cancer and into possible health problems faced by children of mothers who used the OC during pregnancy. Since 1965, women in Japan have been able to obtain prescriptions for high- and medium-dose versions of the OC as treatment for gynecological problems. These formulations are more likely to cause side effects and are, in reality, widely used for contraception. Advocates for the low-dose OC note that issues of safety and effectiveness have been addressed and that the refusal to license the formulation is an attempt to impede the ability of women to control their sexuality and fertility. Some critics point to the irony of the new concern about endocrine disrupters in Japan where dioxins have routinely been released into the atmosphere and waterways as a result of local government waste-control practices. These critics charge that environmentalists have played into the hands of the anti-OC forces by carelessly labeling the OC an endocrine disrupter without scientific proof. While the Japanese government promotes global family planning and population programs, contraceptive options for women in Japan are currently limited to unmedicated IUDs, spermicides, withdrawal, or condoms.^ieng

Goellner v. Butler, 6 January 1988.

PIP: In the case of Goellner vs. Butler, heard in the US Court of Appeals, the plaintiff brought an action against the defendants for negligent insertion of an IUD, which allegedly resulted in her infertility. The Court held that the action was time-barred because the cause of action accrued on the date that the patient was informed of pelvic infection and the erosion of the cervix, but the plaintiff had brought the action more than 10 years after this date, when she learned she was infertile. In 1988, similar rulings were made in cases in Minnesota and Illinois. Other courts held the following in IUD cases: 1) a jury could consider a manufacturer's reasonable conduct in developing unavoidably unsafe but desirable products as well as its unreasonable conduct in not developing an IUD which was as safe as possible; 2) a Food and Drug Administration (FDA) warning linking IUDs to the incidence of pelvic inflammation is admissible as evidence even though the IUD was implanted four months before the effective date of the warning because the regulation containing the warning was adopted one month before the IUD was inserted; and 3) the strict liability, negligence, and breach of warranty claims of states are not specifically preempted by federal laws in the form of warning and design requirements set by the FDA. In addition, courts in Pennsylvania, Delaware, New Jersey, and Arkansas held that the manufacturers of IUDs had provided sufficient warning to patients in materials provided to prescribing physicians. The Court in Arkansas also held that the exception to the strict liability rule for unavoidably unsafe products which could not be made safe for their intended and ordinary use insulated the manufacturer from liability in design defect cases. In a case relating to the injectable contraceptive Depo-Provera, the District Court of Appeals of Florida held that a plaintiff could not be found contributorily negligent for undergoing a hysterectomy to control bleeding without first considering alternative treatments; and the Court of Appeals of Arizona held that a diaphragm manufacturer's revisions to patient information was admissible as evidence to impeach the manufacturer's credibility.^ieng

Medicolegal issues surrounding Depo-Provera easily overcome.

PIP: Even though the Food and Drug Administration (FDA) does not label Depo-Provera as a contraceptive, this fact should not preclude clinicians from prescribing it as such. The lack of FDA approval may deter clinicians from prescribing Depo-Provera as a contraceptive, but legal precedents for prescribing the drug as a contraceptive do exist. As Dr. Andrew M. Kaunitz of the University of Florida Health Sciences Center explains, it is not uncommon for physicians to prescribe drugs for unlabeled indications. Moreover, the American Medical Association (AMA) maintains that such a practice is entirely proper, as long as it is based on "rational scientific theory, reliable medical opinion, or controlled clinical studies," and as long as the FDA does not mandate that physicians may only prescribe the drug for an officially labeled use. Drug labeling, says the AMA, does not necessarily set the standard for what is good medical practice. Clinicians, however, must take the necessary steps to protect themselves from liability when using Depo-Provera. The AMA warns that official drug labeling may be used as evidence in a liability lawsuit. Through computerized search programs, Kaunitz has investigated US court decisions concerning the use of Depo-Provera as a contraceptive. He found no litigation cases resulting from Depo-Provera's official status with the FDA. He did, however, find lawsuits resulting from physician failure to diagnose pregnancy at the time the patient received Depo-Provera and physician failure to advise the patient about Depo-Provera's side effects--especially the irregular bleeding patterns. Kaunitz advises that informed consent forms should indicate that Depo-Provera is not labeled as a contraceptive in the US and should point out the major side effects.^ieng

Depo-Provera: a critical analysis.

This article discusses the research which has led to the controversy of Depo-Provera, and delineates the risks discovered as a result of the studies. Questions are raised as to the advisability of the continued use of this drug.

PIP: Currently Depo-Provera has not been approved by the FDA (Food and Drug Administration) for contraceptive use in the U.S., although USAID is allowed to distribute it for use in population programs in developing countries. The FDA denied Upjohn's petition for approval of the basis of tests showing that Depo-Provera has caused an increased incidence of mammary carcinoma in laboratory dogs. A review of additional tests conducted on laboratory animals, the results of which were not released to the public, indicates that adverse results were withheld from the public by the manufacturer. Tests with laboratory dogs and monkeys have revealed many serious side effects from the drug. Endometrial carcinoma, shortened life expectancy, interference with carbohydrate metabolism, and suppression of immune responses are the most major of these side effects. The immunosuppressive effects make women more vulnerable to infection and also seem to promote malignancy. Exposure to Depo-Provera, as to other progestogens, in utero is associated with an increased risk of congenital malformation in children. In view of the seriousness of the findings, questions are raised as to the advisability of continued contraceptive use of Depo-Provera.