Pregnancy Drug Risk Categories

PREGNANCY DRUG RISK DEFINITIONS OF RECOMMENDATIONS[1]

COMPATIBLE

The human pregnancy experience, either for the drug itself or drugs in the same class or with similar mechanisms of action, is adequate to demonstrate that the embryo-fetal risk is very low or nonexistent. Animal reproduction data are not relevant.

NO (LIMITED) HUMAN DATA – PROBABLY COMPATIBLE

There may or may not be human pregnancy experience, but the characteristics of the drug suggest that it does not represent a significant risk to the embryo-fetus. For example, other drugs in the same class or with similar mechanisms are compatible or the drug does not obtain significant systemic concentrations. Any animal reproduction data are not relevant.

COMPATIBLE – MATERNAL BENEFIT – EMBRYO – FETAL RISK

There may or may not be human pregnancy experience, but the potential maternal benefit far outweighs the known or unknown embryo-fetal risk. Animal reproduction data are not relevant.

HUMAN DATA SUGGEST LOW RISK

There is limited human pregnancy experience, either for the drug itself of drugs in the same class or with similar mechanisms of action, including the 1st trimester, suggesting that the drug does not represent a significant risk of developmental toxicity (growth restriction, structural anomalies, functional/behavioral deficits, or death) at any time in pregnancy. The limited human pregnancy data outweigh any animal reproduction data.

NO (LIMITED) HUMAN DATA – ANIMAL DATA SUGGEST LOW RISK

Either there is no human pregnancy experience or the few pregnancy exposures have not been associated with developmental toxicity (growth restriction, structural anomalies, functional/behavioral deficits, or death). The drug does not cause developmental toxicity (at doses that did not cause maternal toxicity) in all animal species studied at does < 10 times the human dose based on body surface area of area under the plasma concentration vs. time cure; a measure of the systemic exposure of a drug (AUC).

NO (LIMITED) HUMAN DATA – ANIMAL DATA SUGGEST MODERATE RISK

Either there is no human pregnancy experience or the few pregnancy exposures have not been associated with developmental toxicity (growth restriction, structural anomalies, functional/behavioral, deficits, or death). The drug causes developmental toxicity (at doses that did not cause maternal toxicity) in one animal species at doses < 10 times the human dose based on body surface area or AUC.

NO (LIMITED) HUMAN DATA – ANIMAL DATA SUGGEST RISK

Either there is no human pregnancy experience or the few pregnancy exposures have not been associated with developmental toxicity (growth restriction, structural anomalies, functional/behavioral deficits, or death). The drug causes developmental toxicity (at doses that did not cause maternal toxicity) in two animal species at doses < 10 times the human dose based on body surface area or AUC.

NO (LIMITED) HUMAN DATA – ANIMAL DATA SUGGEST HIGH RISK

Either there is no human pregnancy experience or the few pregnancy exposures have not been associated with developmental toxicity (growth restriction, structural anomalies, functional/behavioral deficits, or death). The drug causes developmental toxicity (at doses that did not cause maternal toxicity) in three or more animal species at doses < 10 times the human dose based on body surface area or AUC.

CONTRAINDICATED – 1ST TRIMESTER

Human exposures in the 1st trimester, either to the drug itself or to drugs in the same class or with similar mechanisms of action, have been associated with developmental toxicity (growth restriction, structural anomalies, functional/behavioral deficits, or death). The drug should be used in the 1st trimester.

CONTRAINDICATED – 2ND AND 3RD TRIMESTERS

Human exposures in the 2nd and 3rd trimesters, either to the drug itself or to drugs in the same class or with similar mechanisms of action, have been associated with developmental toxicity (growth restriction, structural anomalies, functional/behavior deficits, or death). The drug should not be used in the 2nd and 3rd trimesters.

CONTRAINDICATED

Human exposures at any time in pregnancy, either to the drug itself or to drugs in the same class or with similar mechanisms of action, have been associated with developmental toxicity (growth restriction, structural anomalies, functional/behavioral deficits, or death). Animal reproduction data, if available, confirm the risk. The drug should not be used in pregnancy.

NO (LIMITED) HUMAN DATA – NO RELEVANT ANIMAL DATA

There is no human pregnancy data or relevant data in animals, or the human pregnancy experience, that may or may not include the 1st trimester, is limited. The risk in pregnancy cannot be assessed.

HUMAN DATA SUGGEST RISK IN 1ST TRIMESTER

Evidence (for the drug or similar drugs) suggests that there may be an embryo-fetal risk for developmental toxicity (growth restriction, structural anomalies, functional/behavioral deficits, or death) in the 1st trimester but not in the 2nd and 3rd trimesters. The human pregnancy data outweigh any animal reproduction data.

HUMAN DATA SUGGEST RISK IN 1ST AND 3RD TRIMESTERS

Evidence (for the drug or similar drugs) suggests that there may be an embryo-fetal risk for developmental toxicity (growth restriction, structural anomalies, functional/behavioral deficits, or death) in the 1st and 3rd trimesters but not in the 2nd trimester. The human pregnancy data outweigh any animal reproduction data.

HUMAN DATA SUGGEST RISK IN 2ND AND 3RD TRIMESTERS

Evidence (for the drug or similar drugs) suggests that there may be a fetal risk for developmental toxicity (growth restriction, structural anomalies, functional/behavioral deficits, or death) in the 2nd and 3rd trimesters but not in the 1st trimester. The human pregnancy data outweigh any animal reproduction data.

HUMAN DATA SUGGEST RISK IN 3RD TRIMESTER

Evidence (for the drug or similar drugs) suggests that there may be a fetal risk for developmental toxicity (growth restriction, structural anomalies, functional/behavioral deficits, or death) in the 3rd trimester, or close to delivery but not in the 1st or 2nd trimesters. The human pregnancy data outweigh any animal reproduction data.

HUMAN (AND ANIMAL) DATA SUGGEST RISK

The human data for the drug or drugs in the same class or with the same mechanism of action, and animal reproduction data if available, suggest there may be a risk for developmental toxicity (growth restriction, structural anomalies, functional/behavioral deficits or death) throughout pregnancy. Usually, pregnancy exposure should be avoided, but the risk may be acceptable if the maternal condition requires the drug.
[1] Briggs, Gerald G., Freeman, Roger K. (2015) Drugs in Pregnancy and Lactation Tenth Edition.