8.1Pregnancy Risk Summary
Limited published data on epinephrine use in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. However, there are risks to the mother and fetus associated with epinephrine use during labor or delivery, and risks due to untreated hypotension associated with septic shock (see Clinical Considerations) . In animal reproduction studies, epinephrine demostrated adverse developmental effects when administed to pregnant rabbits (gastroschisis), mice (teratogenie effects, embryonic lethality, and delayed skeletal ossification), and hamsters (embryonic lethality and delayed skeletal ossification) during organogenesis at doses approximately 15 times, 3 times and 2 times, respectively, the maximum recommended daily intramuscular or subcutaneous dose (see Data).
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Hypotension associated with septic shock is a medical emergency in pregnancy which can be fatal if left untreated.
Delaying treatment in pregnant women with hypotension associated with septic shock may increase the risk of maternal and fetal morbidity and mortality. Do not withhold life-sustaining therapy for a pregnant woman. Labor or Delivery Epinephrine usually inhibits spontaneous or oxytocin-induced contractions of the pregnant human uterus and may delay the second stage of labor. Avoid epinephrine during the second stage of labor.
In dosage sufficient to reduce uterine contractions, the drug may cause a prolonged period of uterine atony with hemorrhage. Avoid epinephrine in obstetrics when maternal blood pressure exceeds 130/80 mmHg. Although epinephrine may improve maternal hypotension associated with septic shock and anaphylaxis, it may result in uterine vasoconstriction, decreased uterine blood flow, and fetal anoxia. Data Animal Data In an embryofetal development study with pregnant rabbits dosed during the period of organogenesis (on days 3 to 5, 6 to 7, or 7 to 9 of gestation), epinephrine caused teratogenic effects (including gastroschisis) at doses approximately 15 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 1.2 mg/kg/day for 2 to 3 days).Animals treated on days 6 to 7 had decreased number of implantations.
In an embryofetal development study, pregnant mice were administered epinephrine (0.1 to 10 mg/kg/day) on Gestation Days 6 to 15. Teratogenic effects, embryonic lethality, and delays in skeletal ossification were observed at approximately 3 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m 2 basis at maternal subcutaneous dose of 1 mg/kg/day for 10 days). These effects were not seen in mice at approximately 2 times the maximum recommended daily intramuscular or subcutaneous dose (on a mg/m 2 basis at a subcutaneous maternal dose of 0.5 mg/kg/day for 10 days).
In an embryofetal development study with pregnant hamsters dosed during the period of organogenesis from gestation days 7 to 10, epinephrine produced reductions in litter size and delayed skeletal ossification at doses approximately 2 times the maximum recommended intramuscular, subcutaneous, or intravenous dose (on a mg/m 2 basis at a maternal subcutaneous dose of 0.5 mg/kg/day).
