Drugs in Pregnancy

Pregnancy is a unique period in a woman’s life. Many changes are happening to her body that may affect the pharmacology of medications. During pregnancy, a woman’s gastric pH is increased and gastric motility is reduced which may interfere with the rate and extent of medication absorption. Maternal plasma volume is increased leading to changes in the volume of distribution. In addition, increases in progesterone and estradiol levels may affect the hepatic metabolism of some medications. Glomerular filtration rate is increased due to increase renal blood flow which may affect renally cleared medications.

Despite the changes, the pharmacology of most medications is not altered enough to require dosing changes. The placenta is an organ of exchange allowing the mother to pass nutrients and medications to the fetus; therefore, medications administered to pregnant women have the potential to affect the growing fetus. The fetus is generally at the greatest risk of developing teratogenic effects from medications during the first trimester, but it is drug specific. The use of medications in pregnancy should be evaluated for the benefits and risks to both the mother and fetus. Upon evaluation, some medications may be used sparingly during some trimesters and contraindicated in others. All efforts should be made to optimize the risk benefit ratio.
Drugs with low molecular weight, low maternal protein binding, low ionization, and high lipophilicity are more likely to cross the placenta and cause pharmacologic affects.1 The developing fetus’s body systems are not mature; therefore, the fetus may lack the ability to metabolize medications causing teratogenic effects.

The FDA has categorized the potential teratogenic risk of medications by an A, B, C, D, X system.

Category A:

Controlled studies in women have failed to demonstrate a risk to the fetus in the first trimester and there is no evidence of risk in later trimesters. The possibility of fetal harm appears remote. Medications in this class are considered safe to use in pregnancy. Examples of medications in this class are vitamins and levothyroxine.

Category B:

Either animal‐reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women, or animal studies have demonstrated risk to the fetus that was not confirmed in controlled studies in pregnant women in the first trimester and there is no evidence of a risk in later trimesters. Medications in this class are generally considered safe. Examples of medications in this class
are acetaminophen and amoxicillin.

Category C:

Studies in animals have revealed adverse effects on the fetus and there are no controlled studies in women, or studies in women and animals are not available. Drugs from this class can be given to pregnant women if the benefit to the mother outweighs the risk to the fetus. Examples of medications in this class are diltiazem and spironolactone.

Category D:

Evidence of human fetal risk has been documented, but the benefits to the mother may be acceptable despite the risk to the fetus. Drugs in this class may be used in pregnancy if the benefits to the mother outweigh the risk to the fetus (i.e. a life threatening situation or a serious disease for which safer medication cannot be used or are not efficacious). Examples of medications in this class are phenytoin and valproic acid.

Category X:

Studies in animals or humans have demonstrated teratogenic effects. The risk to the fetus clearly outweighs any potential benefit to the mother. Drugs in this category are contraindicated in pregnancy. Examples of medications in this class are thalidomide and warfarin.