Sarecycline is an oral, once daily, narrow spectrum tetracycline used to treat moderate-to-severe acne. Oral sarecycline use has been rarely linked to serum enzyme elevations during therapy and, although suspected of causing liver injury, it has yet to be linked to clinically apparent acute hepatic injury.
Sarecycline (sar" e sye' kleen) is an oral, narrow spectrum tetracycline antibiotic with potent activity against Propionbacterium acnes, a gram-positive organism that plays an important role in the inflammatory lesions of acne vulgaris. The tetracyclines act by inhibition of protein synthesis by binding to the 30S subunit of microbial ribosomes. Human cells are less susceptible to this inhibition. Tetracyclines have been available in the United States since the 1957s and used in therapy of several bacterial infections as well as acne. More modern forms of tetracycline include doxycycline, minocycline and sarecycline which have better absorption and tissue penetration. Sarecycline also has a more limited spectrum of antibacterial activity and was developed specifically for therapy of acne and to avoid the broad spectrum complications such as Clostridium difficile colitis. Sarecycline was approved for use in moderate-to-severe acne in 2018 and is available in tablets of 60, 100 and 150 mg under the brand name Seysara. The recommended dose is based upon body weight and administered as a single tablet once daily (60 mg for 33-54 kg; 100 mg for 55-84 kg; and 150 mg for 85-136 kg). Typically, chronic long term and sometimes intermittent therapy is used for acne. Common side effects of sarecycline include gastrointestinal upset, nausea, poor appetite, diarrhea, glossitis, rash and hypersensitivity reactions. Tetracyclines can cause vertigo and tinnitus, skin photosensitivity reactions, and staining of developing teeth (in children or when taken by a pregnant mother) for which reason the tetracyclines should not be used in pregnant women or in children below the age of nine.
In preclinical clinical trials of sarecycline in facial acne, serum aminotransferase elevations were mild and no more frequent than with placebo or comparator arms. There were no instances of clinically apparent liver injury. Nevertheless, other tetracycline antibiotics, even when used in low doses, are well known causes of drug induced liver injury particularly when given long term. Minocycline which is also used for acne is one of the most common causes of liver injury with jaundice. The injury typically arises after months or years of therapy and frequently presents as an autoimmune-like syndrome that can mimic lupus erythematosus, rheumatoid arthritis or autoimmune hepatitis. While sarecycline has not been associated with a similar syndrome, it has been available for a short time only, and the prelicensure clinical trials were generally for 12 weeks only.
Likelihood score: E* (unproven but suspected cause of clinically apparent liver injury).
Mechanism of Injury
The mechanism by which sarecycline might cause liver injury is unknown. It has minimal hepatic metabolism and is not associated with significant drug-drug interactions. Minocycline associated liver injury and has been shown to have an association with carriage of the rare HLA allele B*35:02.
Outcome and Management
Patients on long term sarecycline who develop serum aminotransferase elevations should be monitored more carefully and, if ALT or AST rise above 5 times the upper limit of normal or are accompanied by jaundice or symptoms (including arthralgias and rash), sarecycline should be discontinued. Whether there is cross sensitivity to hepatic injury among the various tetracyclines is not known, but switching to another tetracycline after drug induced liver injury from another should be done with caution and careful monitoring.
Drug Class: Antiinfective Agents, Tetracyclines
Sarecycline – Seysara®
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