Deflazacort

Moderate or strong CYP3A4 inhibitors: Give one third of the recommended dosage of JAYTHARI ( 7.1 ) Avoid use of moderate or strong CYP3A4 inducers with JAYTHARI, as they may reduce efficacy ( 7.1)

7.1 CYP3A4 Inhibitors and Inducers Moderate or Strong CYP3A4 Inhibitors The active metabolite of deflazacort, 21-desDFZ, is a substrate of CYP3A4 [see Clinical Pharmacology (12.3) ] . Co-administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold. Therefore, give one third the recommended dosage of JAYTHARI when moderate or strong CYP3A4 inhibitors (e.g., clarithromycin, fluconazole, diltiazem, verapamil, grapefruit juice) are used concomitantly with deflazacort [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] .

Moderate or Strong CYP3A4 Inducers Co-administration of deflazacort with rifampin, a strong CYP3A4 inducer, significantly decreased the exposure of 21-desDFZ. Avoid concomitant use of strong (e.g., efavirenz) or moderate (e.g., carbamazepine, phenytoin) CYP3A4 inducers with deflazacort [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3) ] .

7.2 Neuromuscular Blockers Patients receiving corticosteroids, including JAYTHARI, and concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium) may be at increased risk of developing an acute myopathy [see Warnings and Precautions (5.11) ] .

8.1 Pregnancy Risk Summary Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism. There are no adequate and well-controlled studies with deflazacort in pregnant women to inform drug-associated risks. Corticosteroids, including deflazacort, readily cross the placenta.

Adverse developmental outcomes, including orofacial clefts (cleft lip, with or without cleft palate) and intrauterine growth restriction, and decreased birth weight, have been reported with maternal use of corticosteroids, including deflazacort, during pregnancy. Some epidemiologic studies report an increased risk of orofacial clefts from about 1 per 1,000 infants to 3 to 5 per 1,000 infants; however, a risk for orofacial clefts has not been observed in all studies. Intrauterine growth restriction and decreased birth weight appear to be dose-related; however, the underlying maternal condition may also contribute to these risks (see Data) .

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. 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. Animal reproduction studies have not been conducted with deflazacort. Animal reproduction studies conducted with other corticosteroids in pregnant mice, rats, hamsters, and rabbits using clinically relevant doses have shown an increased incidence of cleft palate.

An increase in embryofetal death, intrauterine growth retardation, and constriction of the ductus arteriosus were observed in some animal species. Data Human Data Multiple cohort and case-controlled studies in humans suggest that maternal corticosteroid use during the first trimester increases the rate of cleft lip, with or without cleft palate, from about 1/1,000 infants to 3 to 5/1,000 infants. Two prospective case-controlled studies showed decreased birth weight in infants exposed to maternal corticosteroids in utero.