Instructions for Use of the Reference Guide]]>
Each monograph contains six parts:
- Generic Name (United States)
- Pharmacologic Class
- Risk Factor
- Fetal Risk Summary
- Breast Feeding Summary
- References (some monographs have none)
Fetal Risk Summary
The Fetal Risk Summary is a brief review of the literature concerning the drug. The intent of the Summary is to provide clinicians and others with sufficient data to counsel patients and to arrive at conclusions on the risk:benefit ratio a particular drug poses for the fetus. The molecular weights of most drugs have been included in the reviews because they help determine if a drug can reach the embryo or fetus, but this value, by itself, may not predict the amount of transfer. The major determinant of the drug concentration in the embryo or fetus is the blood concentration of the drug in the mother. Other important factors include placental blood flow, the placental surface area available for transfer (i.e., correlated to the gestational age), and the lipid solubility, protein binding, and amount of ionization of the drug at physiologic pH.
Because few absolutes are possible in the area of human teratology, the reader must carefully weigh the evidence, or lack thereof, before utilizing any drug in a pregnant woman. Readers who require more details than are presented should refer to the specific references listed at the end of the monograph.
Breast Feeding Summary
The Breast Feeding Summary is a brief review of the literature concerning the passage of the drug into human breast milk and the effects, if any, on the nursing infant. In many studies of drugs in breast milk, infants were not allowed to breast feed. Readers should pay close attention to this distinction (i.e., excretion into milk vs. effects on the nursing infant) when using a Summary. Those who require more details than are presented should refer to the specific references listed at the end of the monograph.
Risk Factors (A, B, C, D, X) have been assigned to all drugs, based on the level of risk the drug poses to the fetus. Risk Factors are designed to help the reader quickly classify a drug for use during pregnancy. They do not refer to breast feeding risk. Because they tend to oversimplify a complex topic, they should always be used in conjunction with the Fetal Risk Summary. The definitions for the Factors are those used by the Food and Drug Administration (Federal Register 1980;44:37434Ц67). Many older drugs have not been given a letter rating by their manufacturers, and the Risk Factor assignments were made by the authors. If the manufacturer rated its product in its professional literature, the Risk Factor will be shown with a subscript M (e.g., CM). If the manufacturer and the authors differed in their assignment of a Risk Factor, our Risk Factor is marked with an asterisk and the manufacturer’s rating is shown at the end of the Fetal Risk Summary. Other Risk Factors marked with an asterisk (e.g., sulfonamides, morphine, etc.) are drugs that present different risks to the fetus, depending on when or for how long they are used. In these cases, a second Risk Factor will be found with a short explanation at the end of the Fetal Risk Summary. We hope this will increase the usefulness of these ratings. The definitions used for the Risk Factors are presented below.
Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester (and there is no evidence of a risk in later trimesters), and the possibility of fetal harm appears remote.
Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters).
Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.
There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Studies in animals or human beings have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.
Comparison of Agents Within the Same Pharmacologic Class
The Appendix arranges the drugs by their pharmacologic category. This allows the reader to identify all of the drugs that have been reviewed within a specific category, thus allowing, if desired, a comparison of the drugs. For example, the subsection Antihypertensives lists together those agents used for this purpose under the general heading Cardiovascular Drugs. To assist the reader in locating an agent in the Appendix, page numbers (in parentheses) referring to the location in the Appendix have been added to the generic names (shown in bold) in the Index.