False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.
Tetracycline-class drugs, including EMROSI, may cause permanent discoloration of deciduous teeth and reversible inhibition of bone growth when administered during the second and third trimesters of pregnancy [see Warnings and Precautions (5.2, 5.3)and Use in Specific Populations (8.4)]. A few postmarketing cases of limb reductions have been reported over decades of use; however, the association is unclear. The limited data from postmarketing reports are not sufficient to inform a drug-associated risk for birth defects or miscarriage.
In animal reproduction studies conducted in pregnant rats and rabbits, bent limb bones were observed following oral administration of minocycline hydrochloride during organogenesis at systemic exposure of approximately 7.1 and 4.8 times, respectively, the maximum recommended human dose (MRHD) based on AUC exposures (see Data).
If the patient becomes pregnant while taking this drug, advise the patient of the risk to the fetus and discontinue treatment.
The 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 U.S. 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.
The use of tetracycline class drugs, including EMROSI, during tooth development (second and third trimesters of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of deciduous teeth (yellow-gray-brown). Permanent discoloration of the teeth is more common during long-term use of the drug but has been observed following repeated short-term courses [see Warnings and Precautions (5.2)].
Animal Data
Results of animal studies indicate that minocycline hydrochloride crosses the placenta, are found in fetal tissues, and can cause delayed skeletal development in the developing fetus. Evidence of embryotoxicity has been noted in animals treated early in pregnancy [see Warnings and Precautions (5.3)].
Minocycline hydrochloride induced skeletal malformations (bent limb bones) in fetuses when administered to pregnant rats and rabbits during the period of organogenesis at doses of 30 mg/kg/day and 100 mg/kg/day, respectively, (7.1 and 4.8 times, respectively, the MRHD based on AUC comparison). Reduced mean fetal body weight was observed in studies in which minocycline hydrochloride was administered to pregnant rats at an oral dose of 10 mg/kg/day (2.4 times the MRHD based on AUC comparison).
Minocycline hydrochloride was assessed for effects on peri- and post-natal development of rats in a study that involved oral administration to pregnant rats during the period of organogenesis through lactation at doses of 5, 10, or 50 mg/kg/day. In this study, body weight gain was significantly reduced in pregnant females that received 50 mg/kg/day (6 times the MRHD based on AUC comparison). No effects of treatment on the duration of the gestation period or the number of live pups born per litter were observed. Gross external anomalies observed in offspring of animals that received minocycline hydrochloride at 50 mg/kg/day included reduced body size, improperly rotated forelimbs, and reduced size of extremities. No effects were observed on the physical development, behavior, learning ability, or reproduction of the offspring of animals that received minocycline hydrochloride.