Succimer

Contraindications

4 CONTRAINDICATIONS CHEMET is contraindicated in patients with a history of hypersensitivity reaction to succimer. Reactions have included mucocutaneous vesicular eruptions, urticaria, and angioedema [see Warnings and Precautions (5.1) ] . Patients with a history of hypersensitivity reaction to succimer. ( 4 )

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary There are no studies with the use of CHEMET in pregnant women to inform drug-associated risks. Administration of CHEMET to pregnant mice during organogenesis at dose exposure of 11-times the human exposure at the maximum recommended human dose (MRHD) of 700 mg based on body surface area (BSA) resulted in maternal toxicity and mortality and impaired reflex development in offspring (see Animal Data ) . There are adverse effects on maternal and fetal outcomes associated with lead poisoning in pregnancy (see Clinical Considerations ) . CHEMET should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. However, the background risk in the U.S general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Lead exposure in pregnancy may increase the risk of gestational hypertension. Lead crosses the placenta in amounts related to maternal plasma levels. Prenatal lead exposure may be associated with spontaneous abortion, preterm delivery, decreased birth weight, and impaired neurodevelopment. Data Animal Data In embryo-fetal developmental studies, pregnant mice received subcutaneous succimer during the period of organogenesis at doses up to 1640 mg/kg/day (11-times the MRHD based on BSA) which resulted in both maternal and fetal toxicity. In a developmental study in rats, dosing with succimer during the period of organogenesis resulted in maternal toxicity and deaths at the dose of 720 mg/kg/day (10-times the MRHD based on BSA) or more. The dose of 510 mg/kg/day (7-times the MRHD based on BSA) was the highest tolerable dose in pregnant rats. Impaired development of reflex