Sarecycline

Oral retinoids: avoid coadministration. ( 5.4 , 7.1 ) Antacids and iron preparations: separate dosing of SEYSARA. ( 7.1 ) Penicillin: avoid coadministration. ( 7.2 ) Anticoagulants: decrease anticoagulant dosage as appropriate. ( 7.2 ) P-glycoprotein substrates: monitor for toxicities of drugs that may require dosage reduction. ( 7.2 )

7.1 Effect of Other Drugs on SEYSARA Oral Retinoids Tetracyclines may cause increased intracranial pressure as do oral retinoids, including isotretinoin and acitretin [see Warnings and Precautions ( 5.4 )] . Avoid coadministration of SEYSARA with oral retinoids. Antacids and Iron Preparations Coadministration with antacids containing aluminum, calcium or magnesium, bismuth subsalicylate, and iron-containing preparations may impair absorption of SEYSARA, similar to other tetracyclines, which may decrease its efficacy. Separate dosing of SEYSARA from antacids containing aluminum, calcium or magnesium, bismuth subsalicylate, and iron-containing preparations.

7.2 Effect of SEYSARA on Other Drugs Penicillin Similar to other tetracyclines, SEYSARA may interfere with the bactericidal action of penicillin. Avoid coadministration of SEYSARA with penicillin. Anticoagulants Similar to other tetracyclines, SEYSARA may depress plasma prothrombin activity, which may increase the risk of bleeding in patients who are on anticoagulant therapy. Decrease anticoagulant dosage when coadministered with SEYSARA as appropriate. P-Glycoprotein (P-gp) Substrates Concomitant use of SEYSARA may increase concentrations of concomitantly administered P-gp substrates (e.g. digoxin).

Monitor for toxicities of drugs that are P-gp substrates and may require dosage reduction when given concurrently with SEYSARA [see Clinical Pharmacology ( 12.3 )] . Oral Hormonal Contraceptives There is no clinically significant effect of SEYSARA on the efficacy of oral contraceptives containing ethinyl estradiol and norethindrone acetate [see Clinical Pharmacology ( 12.3 )] .

8.1 Pregnancy Risk Summary SEYSARA, like tetracycline class drugs, may cause fetal harm, permanent discoloration of teeth, and reversible inhibition of bone growth when administered during pregnancy [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.4 )] . The limited available human data are not sufficient to inform a drug-associated risk for birth defects or miscarriage. Tetracyclines are known to cross the placental barrier; therefore, SEYSARA may be transmitted from the mother to the developing fetus.

In animal reproduction studies, sarecycline induced skeletal malformations in fetuses when orally administered to pregnant rats during the period of organogenesis at a dose 1.4 times the maximum recommended human dose (MRHD) of 150 mg/day (based on AUC comparison). When dosing with sarecycline continued through the period of lactation, decreases in offspring survival, offspring body weight, and implantation sites and viable embryos in offspring females occurred at a dose 3 times the MRHD (based on AUC comparison) [see Data ] .

The potential risk to the fetus outweighs the potential benefit to the mother from SEYSARA use during pregnancy; therefore, pregnant patients should discontinue SEYSARA as soon as pregnancy is recognized. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population 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.

Data Animal Data In an embryofetal developmental study in rats, sarecycline was administered to pregnant rats at oral doses up to 500 mg/kg/day during the period of organogenesis. Decreases in maternal body weight, fetal body weight and litter size and increases in the number of resorption and postimplantation loss occurred at 500 mg/kg/day (7 times the MRHD based on AUC comparison). Skeletal malformations (bent forelimb, hindlimb, and scapula) occurred at all dose levels (≥ 50 mg/kg/day, 1.4 times the MRHD based on AUC comparison).

In an embryofetal developmental study in rabbits, sarecycline was administered to pregnant rabbits at oral doses up to 150 mg/kg/day during the period of organogenesis. Excessive maternal toxicity (mortality/moribundity/abortion) occurred at 150 mg/kg/day (5 times the MRHD based on AUC comparison) and this dose group was terminated early. Maternal moribundity also occurred at 100 mg/kg/day (0.6 times the MRHD based…