Table 1.
Classification system for fetal risk. FDA classes: in 1979, the United States Food and Drug Administration (FDA) established a five-category classification system for fetal risk from exposure to certain class of medications.
| FDA classification | Definitiona | Examples |
|---|---|---|
| Category A | Controlled studies in women fail to demonstrate a risk to fetus. The possibility of harm to the fetus appears remote. | Multivitamins |
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| Category B | Either animal studies have not demonstrated a fetal risk but there are no controlled human studies or animal studies have indicated an adverse effect that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of risk in the later trimesters). | (i) PO acetaminophen (ii) Opioids: nalbuphine (iii) Local anesthetic: lidocaine |
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| Category C | Teratogenic or embryocidal risk indicated in animal studies, but controlled studies in women have not been done or there are no controlled studies in animals or humans. | (i) NSAIDs: sulindac, naproxen (ii) Opioids: codeine, butorphanol, fentanyl, hydrocodone, levorphanol, methadone, morphine, oxycodone, and oxymorphone (iii) Antidepressants: fluoxetine (iv) Tricyclic antidepressants: amitriptyline, imipramine (v) Anticonvulsant: gabapentin (vi) Drugs used for migraine: metoprolol, propranolol, sumatriptan, nifedipine, and verapamil |
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| Category D | Positive evidence of fetal risk, but use in pregnant woman is acceptable since the maternal benefit outweighs the risk to the fetus. | (i) NSAIDs: aspirin (ii) Steroids: cortisone (iii) Anticonvulsants: diazepam, phenobarbital, and phenytoin |
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| Category X | Animal and human studies demonstrate fetal abnormalities or there is evidence of fetal risk based on human experience or both; the risk outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant. | (i) Antimigraine: ergotamine (ii) Antidepressants: paroxetine (iii) Anticonvulsants: valproic acid |
aThe definitions for the factors are derived from those used by the FDA [15].
In this classification system, all drugs are assigned to risk factor category A, B, C, D, or X based on scientific or clinical evidence of risk to the fetus. They do not refer to breastfeeding risk. A drug is reasonably safe when administered to a pregnant patient if labeled with category A. The FDA classification, however, does not assign any of the pain medications (nonsteroidal anti-inflammatory drugs, opioids, local anesthetics, steroids, tricyclic antidepressants, or antiepileptics) to category A [16, 17].
Despite the lack of literature on the safety of drugs in pregnancy and during lactation, the statistics show that drug use, over the counter and prescription, during pregnancy is widespread. A study published in 2004 found that almost one half of pregnant women received prescription drugs from FDA risk category C, D, or X [18].