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FDA News: Issue 27, October 2018

Published on 10/10/2018 2:51:00 PM


FDA Approves SEYSARA (Sarecycline) for Inflammatory Lesions of Non-Nodular Moderate to Severe Acne Vulgaris in Patients 9 Years of Age and Older

On October 1, 2018, the US Food and Drug Administration (FDA) approved SEYSARA (sarecycline), a tetracycline-class drug, for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 9 years of age and older. The approved recommended dosage of SEYSARA is once daily with or without food as shown below:
  • 60 mg for patients who weigh 33-54 kg 
  • 100 mg for patients who weigh 55-84 kg
  • 150 mg for patients who weigh 85-136 kg
 
Administer SEYSARA with adequate amounts of fluid to reduce the risk of esophageal irritation and ulceration. Efficacy of SEYSARA beyond 12 weeks and safety beyond 12 months have not been established. If there is no improvement after 12 weeks, reassess treatment with SEYSARA. To reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of other antibacterial drugs, SEYSARA should be used only as indicated. SEYSARA has not been evaluated in the treatment of infections. 
 
Mechanism of Action (MOA) and Pharmacokinetics (PK) 
  • MOA: The mechanism of action of SEYSARA in treating acne vulgaris is not known. 
  • General PK: Increasing the SEYSARA dose from 60 to 150 mg once daily in healthy subjects resulted in a slightly less than proportional increase in sarecycline steady-state Cmax and AUCtau. A mean accumulation ratio of sarecycline ranges from 1.5- to 1.6-fold with repeated dosing. Steady-state of sarecycline was reached by Day 7.
  • Absorption: The median Tmax of sarecycline is 1.5 to 2.0 hours. 
  • Distribution: Protein binding of sarecycline is 62.5% to 74.7% in vitro. The mean apparent volume of distribution of sarecycline at steady-state ranges from 91.4 L to 97.0 L.
  • Elimination: The mean apparent oral clearance (CL/F) of sarecycline at steady state is approximately 3 L/h. The mean elimination half-life of sarecycline is 21 to 22 hours.
  • Metabolism: Metabolism of sarecycline by enzymes in human liver microsomes is < 15% in vitro.
  • Excretion: After a single 100 mg oral dose of radiolabeled sarecycline, 42.6% of the dose was recovered in feces (14.9% as unchanged) and 44.1% in urine (24.7% as unchanged).
Drug Interactions
  • Oral Retinoids: Tetracyclines may cause increased intracranial pressure as do oral retinoids, including isotretinoin and acitretin. 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.
  • Penicillin: Similar to other tetracycline, 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 P-gp substrates (e.g., digoxin). Monitor for toxicities, and dosage reduction may be required for drugs that are P-gp substrates when used concomitantly with SEYSARA.
Use in Specific Populations
No clinically significant differences in the pharmacokinetics of sarecycline were observed based on age (11 to 73 years), weight (42 to 133 kg), sex, renal impairment, or mild to moderate hepatic impairment (Child Pugh A to B). The effect of end-stage renal disease (ESRD) or severe hepatic impairment (Child-Pugh C) on sarecycline pharmacokinetics has not been assessed.

Efficacy and Safety
Efficacy of once daily SEYSARA was assessed in two 12-week multicenter, randomized, double-blind, placebo-controlled studies in subjects 9 years of age and older. The two co-primary efficacy endpoints were the percentage of subjects with Investigator's Global Assessment (IGA) success and absolute reduction from baseline in inflammatory lesion counts at Week 12. Additional information regarding efficacy trials can be found in the full prescribing information linked below.
 
Most common adverse reaction (incidence ≥ 1%) is nausea.
 
Full prescribing information is available at https://go.usa.gov/xPKdS
 
Visit Drugs@FDA at http://go.usa.gov/cMsjT for prescribing and patient information, approval letters, reviews and other information for FDA-approved drug products, which are often available shortly following approval. 

A non-comprehensive list of examples of clinical substrates, inhibitors and inducers for metabolic and transporter system related interactions may be found at https://go.usa.gov/xXY9C.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA's MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178), or by mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.

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