Seysara (Sarecycline Hydrochloride)

SEYSARA^® (sarecycline) tablet, is indicated for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 9 years of age and older.

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

The recommended dosage of SEYSARA is based on body weight described in

Take SEYSARA once daily, with or without food. To reduce the risk of esophageal irritation and ulceration, administer SEYSARA with adequate amounts of fluid.

SEYSARA (sarecycline) tablets:

• 60 mg: capsule-shaped, yellow, film-coated tablets debossed with “S60” on one side and blank on the other side.
• 100 mg: capsule-shaped, yellow, film-coated tablets debossed with “S100” on one side and blank on the other side.
• 150 mg: capsule-shaped, yellow, film-coated tablets debossed with “S150” on one side and blank on the other side.

• Sarecycline, like other tetracycline-class drugs, can cause fetal harm when administered to a pregnant woman. (
  5.1 Teratogenic Effects

  SEYSARA, like other tetracyclines, can cause fetal harm when administered to a pregnant woman. If SEYSARA is used during pregnancy or if the patient becomes pregnant while taking SEYSARA, the patient should be informed of the potential hazard to the fetus and treatment should be stopped immediately.

  The use of drugs of the tetracycline-class during tooth development (second and third trimesters of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of these drugs, but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported.

  All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in premature human infants given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued. Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can cause retardation of skeletal development on the developing fetus. Evidence of embryotoxicity has been noted in animals treated with SEYSARA during pregnancy in association with maternal toxicity

  [see Use in Specific Populations ]

  .
  ,
  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 and Use in Specific Populations ]

  . 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 on AUC comparison). No significant embryofetal toxicity or malformations were observed at doses up to 100 mg/kg/day (0.6 times the MRHD based on AUC comparison).

  In a pre- and post-natal developmental study in rats, sarecycline was administered to maternal rats at oral doses up to 400 mg/kg/day during the period of organogenesis through lactation. Excessive litter toxicity (litter loss and stillbirth) occurred at 400 mg/kg/day (8 times the MRHD based on AUC comparison), which led to early termination of dams at parturition. Decreases in body weight and food consumption of dams during the lactation period occurred at 150 mg/kg/day (3 times the MRHD based on AUC comparison). Decreases in offspring survival and offspring body weight during the preweaning and growth period, and decreases in implantation sites and viable embryos in female offspring occurred at 150 mg/kg/day (3 times the MRHD based on AUC comparison). No significant maternal or developmental toxicity was observed at 50 mg/kg/day (1.4 times the MRHD based on AUC comparison).
  )
• The use of drugs of the tetracycline class during tooth development may cause permanent discoloration of teeth. (
  5.1 Teratogenic Effects

  SEYSARA, like other tetracyclines, can cause fetal harm when administered to a pregnant woman. If SEYSARA is used during pregnancy or if the patient becomes pregnant while taking SEYSARA, the patient should be informed of the potential hazard to the fetus and treatment should be stopped immediately.

  The use of drugs of the tetracycline-class during tooth development (second and third trimesters of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of these drugs, but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported.

  All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in premature human infants given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued. Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can cause retardation of skeletal development on the developing fetus. Evidence of embryotoxicity has been noted in animals treated with SEYSARA during pregnancy in association with maternal toxicity

  [see Use in Specific Populations ]

  .
  ,
  8.4 Pediatric Use

  The safety and effectiveness of SEYSARA have been established in pediatric patients 9 years of age and older for the treatment of moderate to severe inflammatory lesions of non-nodular acne vulgaris

  [see Pharmacokinetics and Clinical Studies ]

  .

  Safety and effectiveness of SEYSARA in pediatric patients below the age of 9 years has not been established. Use of tetracycline-class antibiotics below the age of 8 is not recommended due to the potential for tooth discoloration

  [see Warnings and Precautions ]

  .
  )
• Lactation: Breastfeeding is not recommended. (
  8.2 Lactation

  Risk Summary

  Tetracyclines are excreted in human milk. Because of the potential for serious adverse reactions on bone and tooth development in nursing infants from tetracycline-class antibiotics, advise a woman that breastfeeding is not recommended with SEYSARA therapy

  [see Warnings and Precautions ]

  .
  )

• The use of SEYSARA during tooth development (second and third trimesters of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). (
  5.1 Teratogenic Effects

  SEYSARA, like other tetracyclines, can cause fetal harm when administered to a pregnant woman. If SEYSARA is used during pregnancy or if the patient becomes pregnant while taking SEYSARA, the patient should be informed of the potential hazard to the fetus and treatment should be stopped immediately.

  The use of drugs of the tetracycline-class during tooth development (second and third trimesters of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of these drugs, but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported.

  All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in premature human infants given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued. Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can cause retardation of skeletal development on the developing fetus. Evidence of embryotoxicity has been noted in animals treated with SEYSARA during pregnancy in association with maternal toxicity

  [see Use in Specific Populations ]

  .
  )
• If Clostridium difficile Associated Diarrhea (antibiotic associated colitis) occurs, discontinue SEYSARA. (
  5.2

  Clostridium difficile

  Associated Diarrhea (Antibiotic Associated Colitis)

  Clostridium difficile

  associated diarrhea (CDAD) has been reported with nearly all antibacterial agents, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to potential overgrowth of

  C. difficile.

  C. difficile

  produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of

  C. difficile

  cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

  If CDAD is suspected or confirmed, ongoing antibiotic use not directed against

  C. difficile

  should be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of

  C. difficile

  , and surgical evaluation should be instituted as clinically indicated.
  )
• Central nervous system side effects, including light-headedness, dizziness or vertigo, have been reported with tetracycline use. Patients who experience these symptoms should be cautioned about driving vehicles or using hazardous machinery. These symptoms may disappear during therapy and may disappear when the drug is discontinued. (
  5.3 Central Nervous System Effects

  Central nervous system side effects including light-headedness, dizziness or vertigo have been reported with tetracycline use. Patients who experience these symptoms should be cautioned about driving vehicles or using hazardous machinery. These symptoms may disappear during therapy and may disappear when the drug is discontinued.
  )
• SEYSARA may cause intracranial hypertension. Discontinue SEYSARA if symptoms occur. (
  5.4 Intracranial Hypertension

  Intracranial hypertension in adults and adolescents has been associated with the use of tetracyclines. Clinical manifestations include headache, blurred vision and papilledema. Although signs and symptoms of intracranial hypertension resolve after discontinuation of treatment, the possibility for sequelae such as visual loss that may be permanent or severe exists. Women of childbearing age who are overweight have a greater risk for developing intracranial hypertension. Patients should be questioned for visual disturbances prior to initiation of treatment with tetracyclines. Concomitant use of isotretinoin and SEYSARA should be avoided because isotretinoin, a systemic retinoid, is also known to cause intracranial hypertension

  [see Drug Interactions ]

  . If visual disturbance occurs during treatment, patients should be checked for papilledema.
  )
• Photosensitivity can occur with SEYSARA. Patients should minimize or avoid exposure to natural or artificial sunlight. (
  5.5 Photosensitivity

  Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using SEYSARA. If patients need to be outdoors while using SEYSARA, they should wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician.
  )