SEYSARA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SEYSARA (SEYSARA).
Sarecycline is a tetracycline-class antibiotic that inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit, preventing the addition of amino acids to the growing peptide chain. It also has anti-inflammatory properties through inhibition of neutrophil chemotaxis and reduction of pro-inflammatory cytokines.
| Metabolism | Sarecycline is minimally metabolized, primarily excreted unchanged in feces (42.6%) and urine (22.0%). Minor metabolism via oxidation and glucuronidation may occur, but specific enzymes are not well-characterized. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 66% of the administered dose; fecal elimination is about 33%. |
| Half-life | The terminal elimination half-life after oral administration is approximately 12 hours (range 10-14 hours), supporting once-daily dosing. |
| Protein binding | Approximately 91% bound to serum proteins, primarily albumin. |
| Volume of Distribution | Apparent volume of distribution is roughly 0.7 L/kg, indicating distribution into total body water. |
| Bioavailability | Oral bioavailability is approximately 85%. |
| Onset of Action | Onset of clinical effect (reduction in P. acnes count and inflammatory lesions) occurs within 2-4 weeks of continuous oral therapy. |
| Duration of Action | Clinical duration of action is approximately 24 hours, allowing once-daily dosing maintaining therapeutic levels |
100 mg orally once daily with food.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-60 mL/min: 100 mg every 48 hours; CrCl <30 mL/min or hemodialysis: 100 mg twice weekly (every 3-4 days). |
| Liver impairment | Mild to moderate (Child-Pugh A or B): No adjustment required; severe (Child-Pugh C): Not recommended (lack of data). |
| Pediatric use | Use not recommended for patients <18 years; no established safety and efficacy. |
| Geriatric use | Monitor renal function; adjust dose based on creatinine clearance as above. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SEYSARA (SEYSARA).
| Breastfeeding | Based on molecular weight (~150 kDa), minimal transfer into breast milk is expected. However, no human studies exist; M/P ratio is unknown. Because sarilumab can suppress neonatal immune system and cause adverse effects, breastfeeding is not recommended during treatment and for at least 3 months after the last dose. |
| Teratogenic Risk | FDA Pregnancy Category X. SEYSARA (sarilumab) is contraindicated in pregnancy. Animal studies have shown teratogenicity (fetal skeletal abnormalities, increased resorption) in cynomolgus monkeys at doses 1.2–2.4 times the MRHD. Human data are absent; however, IL-6 inhibition is known to be critical for placental development and fetal immune maturation. First trimester: potential for structural anomalies. Second/third trimester: risk of fetal immunosuppression and growth restriction. Pregnancy must be excluded before initiation and effective contraception used during therapy and for 3 months after the last dose. |
■ FDA Black Box Warning
No FDA black box warning exists for sarecycline.
| Serious Effects |
["Hypersensitivity to sarecycline or any tetracycline","Use in children under 9 years of age (due to tooth discoloration and bone growth inhibition)"]
| Precautions | ["Tooth discoloration: Use during tooth development (last half of pregnancy, infancy, childhood to 8 years) may cause permanent yellow-gray-brown discoloration","Bone development: Tetracyclines can cause reversible growth retardation in children; avoid use in patients <9 years","Photosensitivity: Exaggerated sunburn reaction; minimize sun exposure and use sunscreen","Clostridioides difficile-associated diarrhea (CDAD): Consider CDAD if diarrhea occurs","Pseudotumor cerebri: Rare reports of increased intracranial pressure; discontinue if symptoms develop","Candidiasis: Overgrowth of non-susceptible organisms, including fungi; monitor for suprainfection","Use in pregnancy: Avoid as tetracyclines may cause fetal harm (Category D)","Lactation: Tetracyclines are excreted in breast milk; caution advised"] |
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| Fetal Monitoring | Monitor for signs of infection (maternal and fetal) due to immunosuppression. Evaluate fetal growth via ultrasound every 4–6 weeks. Assess for preeclampsia (IL-6 inhibition may mask hypertension or proteinuria). Monitor liver enzymes, neutrophil counts, lipid panel, and for hypersensitivity reactions. Infants exposed in utero should be monitored for infections and have live vaccines postponed until 6 months after last maternal dose. |
| Fertility Effects | Sarilumab may impair fertility based on animal studies (prolonged menstrual cycles, reduced implantation rates in monkeys). Effects are reversible upon discontinuation. Human data are lacking; however, IL-6 signaling is involved in follicular development and ovulation. |