The topics the authors address in this article are in many ways both broad and narrow. The broadness of this topic is clear when one considers the intersection of 2 of the more complex areas in medicine: pharmacology and obstetrics. Many of the common drugs used by dentists have been found to be safe for breastfeeding women; however, consultation with the treating physician may be needed.
Key points
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There is a new labeling system for the safety of medications in pregnant and lactating patients.
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Available data related to the safe use of medications in pregnant and lactating patients are constantly changing.
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The benefits of using a medication must always be weighed against its risks for that patient.
The topics the authors address in this article are in many ways both broad and narrow. The broadness of this topic is clear when one considers the intersection of 2 of the more complex areas in medicine: pharmacology and obstetrics. At the same time when considered in the format of a review article, one can only hope to provide a snapshot of information, which will inevitably change over time. The information provided here is for reference only and the authors suggest consultation with the patients’ obstetrician (or pediatrician for breastfeeding patients) for up-to-date and patient-specific information on a case-by-case basis.
The effect of a medication on a developing fetus depends on many factors. One medication may have a variety of different adverse effects depending on fetal development at the time it is administered. Other considerations include molecular weight of a drug and whether it is lipid or water soluble. Maternal factors, such as altered gastric absorption, may also play a roll.
There are very few known teratogenic medications, and most contraindications to the use of medicaments in gravid patients are relative contraindications only. In other words, rarely is it necessary to prescribe an alternative medication for pregnant patients. The establishment of teratogenicity depends on the meeting of several criteria. Review of these criteria is irrelevant for this article. The reader may refer to Buhimschi and Weiner “Medications in Pregnancy and Lactation: Part 1” for more information. It is important to realize, however, that one of the reasons that there are so few established teratogens is that it is difficult to prove for a particular drug that all criteria have been met for teratogenicity.
The publication of this article coincides with a new labeling system recently instituted by the Food and Drug Administration (FDA). Doctors and patients are both familiar with the grading system instituted by the FDA in 1979 for indicating drug safety in pregnant patients ( Table 1 ).
| Category | Description |
|---|---|
| A | Adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal abnormalities to the fetus in any trimester of pregnancy. |
| B | Animal studies have revealed no evidence of harm to the fetus; however, there are no adequate and well-controlled studies in pregnant women. OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester. |
| C | Animal studies have shown an adverse effect, and there are no adequate and well-controlled studies in pregnant women. OR No animal studies have been conducted, and there are no adequate and well-controlled studies in pregnant women. |
| D | Adequate well-controlled or observational studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy may outweigh the potential risk. For example, the drug may be acceptable if needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective. |
| X | Adequate well-controlled or observational studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities or risks. The use of the product is contraindicated in women who are or may become pregnant. |
There are several problems with this labeling scheme ( Box 1 ). Firstly it oversimplifies the decision-making process for prescribing medications to pregnant patients. By narrowly defining medications within the framework of this system, many practitioners feel limited to prescribing medications in the A and B categories only. Indication for use of a category C drugs often triggers a medical clearance request to the obstetrician often delaying care of patients.
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Delay of care when category C drugs are indicated
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Rigidity of existing system limiting to dentists medical-legally
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Lack of updating based on latest evidence
Secondly, when viewed through a medical-legal lens, this system provides easy fodder for plaintiff’s attorneys to clearly present to a jury supposed evidence of a dentist’s deviation from the standard of care.
Finally, assignment of a medication to a category often becomes a lifetime sentence, as said assignment is seldom updated when new evidence becomes available. This point becomes clear when considering the X designation assigned to triazolam, which has been considered safe for use during pregnancy since the 1990s.
Fortunately, the FDA has recently set forth new guidelines for pregnancy and lactation labeling of medications. This new labeling scheme went into effect on June 30, 2015 and includes sections for both pregnancy and lactation as well as the new category of women and men of reproductive potential. The new labeling scheme will eliminate the long-standing A-B-C-D-X grading system. The pregnancy label, which also includes labor and delivery, will always include a risk summary subsection. A subsection entitled clinical considerations, data, and pregnancy exposure registry will be included when relevant information is available. When the clinical considerations subsection is required, further subsections, such as disease-associated maternal and/or embryo/fetal risk, dose adjustments during pregnancy and the postpartum period, maternal adverse reactions, fetal/neonatal adverse reactions, and labor or delivery, will be included when information is available. The pregnancy exposure registry is a voluntary collection of data collected by physicians and/or pregnant patients who are taking certain medications during pregnancy. The lactation label will include information such as the amount of the drug in breast milk and any potential risk for the child.
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Pregnancy
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Risk summary: always included
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Clinical considerations: when data available
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Disease-associated maternal and/or embryo/fetal risk
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Dose adjustments during pregnancy and the postpartum period
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Maternal adverse reactions
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Fetal/neonatal adverse reactions
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Labor and delivery
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Pregnancy exposure registry: when data available
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Data: when available
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Human data
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Animal data
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Lactation
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Risk summary: always included, must include a risk-benefit statement unless the drug is contraindicated
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Presence of drug in human milk when drug is absorbed systemically
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Effects of drug on the breastfed child when drug is absorbed systemically
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Effects of drug on milk production when drug is absorbed systemically
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Men and women of reproductive age
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Only when indicated
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Although the new rules took effect on June 30, 2015, implementation will take place over a 3- to 5-year period with a total estimated cost of about $78 million. The goal of this significant change in drug labeling as described by the FDA is to “facilitate informed prescribing and safe and effective product use.” This change brings drug labeling for pregnancy and lactation into the twenty-first century and directly addresses the primary issues related to the grading system. Clinical decisions can be made based on information directly on the drug insert. Additionally, this construct encourages the practitioner to make decisions based on updated evidence that may not have made it to print on the drug packaging. This change will, over time, diminish the delay of care related to unnecessary obstetric and pediatric consultations.
The new labeling rule also directly impacts an area that affects all dental practitioners. Many obstetricians recommend that no epinephrine be used in conjunction with local anesthetics during pregnancy. Once this recommendation is made, the dentist’s options for anesthetizing are limited. Some practitioners turn to mepivacaine, which is the same class C category as epinephrine. Alternatively, one may consider lidocaine without an epinephrine additive, which often results in less than adequate anesthesia. The new labeling allows for the unproven possibility of teratogenicity of a medication while also allowing the practitioner to weigh the risks and benefits of the drug for that particular patient. This change frees the dental practitioner to use lidocaine with epinephrine during pregnancy after a risk-benefit analysis and to discuss with patients without the need to tether that decision to an obstetric consultation.
Another area impacted by the labeling change is pain management. Opioid analgesics are commonly prescribed during pregnancy for pain; however, they are currently classified as class C by the FDA, hobbling dental practitioners as with epinephrine. The new labeling rule will allow the dentists more latitude with opioid prescriptions when considering the latest literature in a risk-benefits discussion. Although there is an increased risk of neural tube defects with peri-conception use of some opioids (codeine, hydrocodone, and oxycodone) by about 2%, opioid use during the second trimester is generally considered safe. Caution should be taken during the third trimester because of a risk of newborn opioid dependence. Opioid use can be safely used during the third trimester; however, the obstetrician should be involved so that the newborn can be assessed for dependence after birth.
To summarize, with the activation of a new medication-labeling scheme for pregnant and lactating patients, the FDA has put the decision-making onus back on the individual practitioner. It is always the dentist’s responsibility to be up to date with the constantly changing evidence related to medications and pregnancy. Finally, when considering any medication in any scenario, one must continue to weigh the benefit of using the medication against all possible risks to patients before administering or prescribing it ( Table 2 ).
