孕期及哺乳期颌面外科用药

常用口腔颌面外科药物在孕期和哺乳期应用的安全性

下表摘自参考资料1：

Table	Medication	Use During Pregnancy	Use During Breastfeeding	Previous Letter Classification	Hale Lactation Risk Category	Comments
Local Anesthetics
	Lidocaine	Yes	Yes	B	L2	No evidence of harm
	Mepivacaine	Yes	Yes	C	L3	Risk of methemoglobinemia
	Prilocaine	Yes	Yes	B	Unknown	Risk of methemoglobinemia
	Bupivacaine	No, may cause hypotension	Yes	C	L2	—
	Benzocaine	(Avoid)	Avoid	C	Unknown	Risk of methemoglobinemia
	Articaine	(Avoid)	Avoid	C	Unknown	—
	Epinephrine			C	L1	Reports of fetal malformations with intravenous doses no significant documented risk when used in association with a local anesthetic
Antibiotics
	Amoxicillin	Yes	Yes	B	L1	—
	Penicillin	Yes	Yes	B	L1	—
	Amoxicillin and clavulanate potassium (Augmentin)	Yes	Yes	B	L1	—
	Clindamycin	Yes	Yes	B	L2	Use in the first trimester only if clearly needed
	Azithromycin	(Yes)	Yes, caution (risk-benefit analysis)	B	L2	Avoid in the first trimester
	Erythromycin	Yes	Yes, caution (risk-benefit analysis)	B	L2 L3 early postnatal (pylorus- stenosis!)	Avoid in the first trimester
	Metronidazole (Flagyl)	(Yes)	Yes, caution (risk-benefit analysis)	B	L2	Fetal carcinogen in nonhuman mammals; no proven risk in humans; contraindicated for use in the first trimester as per manufacturer
Analgesics
	Ibuprofen	Avoid in the third trimester; may close PDA	Yes	B	L1	Associated with ductus arteriosus constriction when used during the first trimester
	Aspirin	No, associated with IUGR	Yes	C/D	L3	—
	COX-2 inhibitor	Avoid in the third trimester; may close PDA	Yes	C	L2	—
	Acetaminophen	Yes	Yes	B	L1	Associated with pulmonary hypertension when used in the third trimester
	Opioids (oxycodone, hydrocodone, codeine)	Yes	Yes, caution (risk-benefit analysis), monitor baby	B/C	L3	Frequent use may be associated with a fetal abnormality. First trimester use: low risk of neural tube defects. Third trimester use: risk of fetal dependence and newborn respiratory depression
	Morphine	Yes	Yes	C	L3
	Fentanyl	Yes	Yes	B	L2	Breastfeeding can be resumed when the mother recovers from anesthesia.
Anxiolytics/ Sedatives
	Diazepam (Valium)	No	No	D	L3; L4 if used chronically	Associated with fetal craniofacial and thoracic abnormalities in the first/second trimester
	Triazolam	No	No	X	L3	No known association with fetal abnormalities
	Midazolam	No, risk for fetal craniofacial anomalies	(No)	D	L3	Use near birth associated with adverse neonatal neurobehavior
	Barbiturates	No, risk for fetal craniofacial anomalies		D	L3	——
	Nitrous Oxide	Controversial, avoid in the first trimester	Yes, after recovery from anesthesia	Notassigned	L3	It is generally considered safe in pregnant and nursing patients as long as there is <50% of N2O with supplemental oxygen coadministration. Theoretically, these patients may benefit from prophylactic folic acid, methionine, and vitamin B12. However, it should be avoided in the first trimester.
Steroids						Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects
	Dexamethasone	Avoid in the first trimester	Avoid		L3	Low risk of oral clefts during the first trimester
	Triamcinolone	Avoid in the first trimester	Yes, lack of evidence, alternative preferred	C	L3	Pregnancy: First-trimester risk of oral clefts; continued use may restrict fetal growth; Lactation: As a nasal spray or local injections, such as for tendinitis, it would not be expected to cause any adverse effects.
	Prednisone	Avoid in the first trimester	Yes		L2	Low risk of oral clefts during the first trimester No adverse effect has been reported in breastfed infants with maternal use of any corticosteroid during breastfeeding. With high maternal doses, the use of prednisolone instead of prednisone and avoiding breastfeeding for 4 h after a dose.
Muscle relaxant	Cyclobenzaprine	Yes	Yes, caution (risk-benefit analysis), monitor baby	B	L3	May continue breastfeeding. Monitor the infant for drowsiness, adequate weight gain, and developmental milestones, particularly in neonates and preterm infants.

1. 文中提到的Hale Lactation Risk Category指的是下表的分级：

Hale Lactation risk Category	Safety	Description
L1	Safest	Drug that has been taken by a large number of breastfeeding mothers without any observed increase in adverse effects in the infant. Controlled studies in breastfeeding women fail to demonstrate a risk to the infant and the possibility of harm to the breastfeeding infant is remote, or the product is not orally bioavailable in an infant.
L2	Safer	Drug that has been studied in a limited number of breastfeeding women without an increase in adverse effects in the infant, and/ or the evidence of a demonstrated risk which is likely to follow the use of this medication in a breastfeeding woman is remote.
L3	Moderately safe	There are no controlled studies in breastfeeding women; however, the risk of untoward effects to a breastfed infant is possible, or controlled studies show only minimal nonthreatening adverse effects. Drugs should be given only if the potential benefit justifies the potential risk to the infant.
L4	Possibly hazardous	There is positive evidence of risk to a breastfed infant or breast milk production, but the benefits of use in breastfeeding mothers may be acceptable despite the risk to the infant (eg, 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).
L5	Contraindicated	Studies in breastfeeding mothers have demonstrated that there is a significant and documented risk to the infant based on human experience, or it is a medication that has a high risk of causing significant damage to an infant. The risk of using the drug in breastfeeding women clearly outweighs any possible benefit from breastfeeding. The drug is contraindicated in women who are breastfeeding an infant.

2. 文中提到的Previous Letter Classification指的是FDA旧的A-B-C-D-X分类：

Category A	Adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of a risk in later trimesters)
Category B	Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women
Category C	Animal reproduction studies have shown an adverse effect on the fetus, if there are no adequate and well-controlled studies in humans, and if the benefits from the use of the drug in pregnant women may be acceptable despite its potential risks
Category D	There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but the potential benefits from the use of the drug in pregnant women may be acceptable despite its potential risks
Category X	Studies in animals or humans have demonstrated fetal abnormalities or if there is positive evidence of fetal risk based on adverse reaction reports from investigational or marketing experience, or both, and the risk of the use of the drug in a pregnant woman clearly outweighs any possible benefit

备注：FDA后面出了一个Content and format of labeling for human prescription drug and biological products; requirements for pregnancy and lactation labeling; Final Rule取代了之前的A-B-C-D-X分类

哺乳期用药数据库

LactMed是National Library of Medicine/National Institutes of Health建立的的一个在线参考数据库，提供的一般是最新的数据。

参考资料：

1. Nudell Y, Miller J. Medication for Gravid and Nursing Oral and Maxillofacial Surgery Patients. Oral Maxillofac Surg Clin North Am. 2022 Feb;34(1):201-212. doi: 10.1016/j.coms.2021.08.012. Epub 2021 Oct 30. PMID: 34728146.