Sarecycline
Sarecycline Uses, Dosage, Side Effects, Food Interaction and all others data.
Sarecycline is a semi-synthetic derivative of tetracycline that was initially discovered by Paratek Pharmaceuticals from Boston, MA but then licensed to Warner Chilcott of Rockaway, NJ in July of 2007 . After completing various phase-II and phase-III trials demonstrating its effectiveness in treating moderate to severe facial acne vulgaris the US Food and Drug Administration approved Barcelona based Almirall, S.A.'s Seysara (sarecylcine) as a new first in class narrow spectrum tetracycline derived oral antibiotic for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients nine years of age and older . Seysara (sarecycline) was originally part of Allergan's US Medical Dermatology portfolio, before Almirall acquired the portfolio in the second half of 2018 as a means of consolidating and reinforcing the dermatology-focused pharmaceutical company's presence in the United States .
Acne vulgaris itself is a common chronic skin condition associated with the blockage and/or inflammation of hair follicles and their accompanying sebaceous glands . The acne often presents physically as a mixture of non-inflammatory and inflammatory lesions mainly on the face but on the back and chest as well . Based upon data from Global Burden of Disease studies, the acne vulgaris condition affects up to 85% of young adults aged 12 to 25 years globally - with the possibility of permanent physical and mental scarring resulting from cases of severe acne .
Subsequently, while a number of first line tetracycline therapies like doxycycline and minocycline do exist for treating acne vulgaris, sarecycline presents a new and innovative therapy choice because it exhibits the necessary antibacterial activity against relevant pathogens that cause acne vulgaris but also possesses a low propensity for resistance development in such pathogens and a narrower, more specific spectrum of antibacterial activity, resulting in fewer off-target antibacterial effects on endogenous intestinal flora and consequently fewer resultant adverse effects associated with diarrhea, fungal overgrowth, etc.
| Trade Name | Sarecycline |
| Availability | Prescription only |
| Generic | Sarecycline |
| Sarecycline Other Names | Sareciclina, Sarecycline, Sarécycline, Sarecyclinum |
| Related Drugs | doxycycline, clindamycin topical, erythromycin topical, isotretinoin, tetracycline, Tazorac |
| Weight | 100mg, 150mg, 60mg |
| Type | Oral tablet |
| Formula | C24H29N3O8 |
| Weight | Average: 487.509 Monoisotopic: 487.195464906 |
| Protein binding | The protein binding of sarecycline has been recorded as ranging from 62.5% to 74.7% in vitro . |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Sarecycline is a tetracycline antibiotic used to treat inflammatory lesions of non-nodular moderate to severe acne vulgaris.
Sarecycline is a tetracycline-class drug indicated for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 9 years of age and older .
Sarecycline is also used to associated treatment for these conditions: Moderate, severe Non-nodular acne vulgaris
How Sarecycline works
It has been demonstrated that tetracyclines like sarecycline elicit their antimicrobial action by targeting and inhibiting protein synthesis in microbial agents like Cutibacterium acnes present in acne lesions . In particular, it is believed that sarecycline's mechanism of action revolves around the inhibition of various macromolecular biosynthesis activities like the macromolecular biosynthesis of microbial DNA, RNA, proteins, lipids, and cell wall . Specifically, it has been observed that while sarecycline demonstrates appreciable inhibition of microbial macromolecular DNA and protein synthesis, the compound has little to no effect on lipid biosynthesis, cell wall synthesis, and RNA synthesis . In addition, because Cutibacterium acnes also generates proteins and enzymes that are capable of causing inflammation, it is also believed that tetracyclines like sarecyclines can also affect an anti-inflammatory effect via the inhibition of such microbial protein synthesis .
Toxicity
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 .
In a 2-year oral mouse carcinogenicity study and a 2-year oral rat carcinogenicity study, no drug-related neoplasms were observed in male mice at oral doses of sarecycline up to 100 mg/kg/day (approximately equal to the MRHD based on AUC comparison) or in female mice at doses up to 60 mg/kg/day (approximately equal to the MRHD based on AUC comparison), or in rats at doses up to 200/100 mg/kg/day (dose reduced from 200 to 100 mg/kg/day due to increased mortality; 8 times the MRHD based on AUC comparison) .
Sarecycline was not mutagenic or clastogenic in a series of in vitro and in vivo genotoxicity studies, including a bacteria reverse mutation (Ames) assay, an in vitro chromosomal aberration assay in CHO cells, the L5178Y/TK+/- Mouse Lymphoma Assay, and an in vivo micronucleus assay in rats .
In a fertility and early embryonic development study in rats, sarecycline was administered to both male and female rats at oral doses up to 400 mg/kg/day prior to pairing and through the mating and postmating period . Female fertility was not affected at doses up to 400 mg/kg/day (8 times the MRHD based on AUC comparison) . In sperm evaluation, decreased sperm motility, decreased sperm count and concentration, and an increase in percent abnormal sperm occurred at 400 mg/kg/day (8 times the MRHD based on AUC comparison) . Male fertility was not affected at doses up to 150 mg/kg/day (4 times the MRHD based on AUC comparison) .
Sarecycline, like other tetracycline class drugs, may cause fetal harm, permanent discoloration of teeth, and reversible inhibition of bone growth when administered during pregnancy . 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, sarecycline 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) . The potential risk to the fetus outweighs the potential benefit to the mother from sarecycline use during pregnancy; therefore, pregnant patients should discontinue sarecyclin as soon as pregnancy is recognized .
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 sarecycline therapy .
Avoid using sarecycline in males who are attempting to conceive a child . In a fertility study in rats, sarecycline adversely affected spermatogenesis when orally administered to male rats at a dose 8 times the MRHD (based on AUC comparison) .
The safety and effectiveness of sarecycline 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 . The safety and effectiveness of sarecycline 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 .
Clinical studies of sarecycline did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects .
In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures . Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdose .
Food Interaction
- Take separate from antacids.
- Take with fluids. This may reduce irritation of the esophagus.
- Take with or without food.
Sarecycline multivitamins interaction
[Moderate] GENERALLY AVOID: The bioavailability of oral tetracyclines and iron salts may be significantly decreased during concurrent administration.
Therapeutic failure may result.
The proposed mechanism is chelation of tetracyclines by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract.
In ten healthy volunteers, simultaneous oral administration of ferrous sulfate 200 mg and single doses of various tetracyclines (200 mg to 500 mg) resulted in reductions in the serum levels of methacycline and doxycycline by 80% to 90%, oxytetracycline by 50% to 60%, and tetracycline by 40% to 50%.
In another study, 300 mg of ferrous sulfate reduced the absorption of tetracycline by 81% and that of minocycline by 77%.
Conversely, the absorption of iron has been shown to be decreased by up to 78% in healthy subjects and up to 65% in patients with iron depletion when ferrous sulfate 250 mg was administered with tetracycline 500 mg.
Available data suggest that administration of iron 3 hours before or 2 hours after a tetracycline largely prevents the interaction with most tetracyclines except doxycycline.
Due to extensive enterohepatic cycling, iron binding may occur with doxycycline even when it is given parenterally.
It has also been shown that when iron is administered up to 11 hours after doxycycline, serum concentrations of doxycycline may still be reduced by 20% to 45%.
Coadministration of a tetracycline with any iron-containing product should be avoided if possible.
Otherwise, patients should be advised to stagger the times of administration by at least three to four hours, although separating the doses may not prevent the interaction with doxycycline.
Sarecycline Drug Interaction
Unknown: aripiprazole, amphetamine / dextroamphetamine, loratadine, escitalopram, acetaminophen, desvenlafaxine, cariprazine
Sarecycline Disease Interaction
Volume of Distribution
The mean apparent volume of distribution of sarecycline at steady-state ranges from 91.4 L to 97.0 L .
Elimination Route
The median time to peak plasma concentration (Tmax) of sarecycline is 1.5 to 2.0 hours . When the medication is taken with a meal consisting of high fat (about 50% of total caloric content of the meal), high caloric (about 800 to 1000 Kcal), and milk content the Tmax can be delayed by approximately 0.53 hours and the Cmax and AUC can be decreased by 31% and 27%, respectively .
Half Life
The mean elimination half-life of sarecycline is 21 to 22 hours .
Clearance
The mean apparent oral clearance (CL/F) of sarecycline at steady state is about 3 L/h .
Elimination Route
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) .
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