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Sarecycline

Class: Aminomethylcyclines
Chemical Name: (4S,4aS,5aR,12aS)-4-(Dimethylamino)-3,10,12,12a-tetrahydroxy-7-[(methoxymethylamino) methyl]-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide monohydrochloride
Molecular Formula: C24H29N3O8•HCl
CAS Number: 1035979-44-2
Brands: Seysara

Medically reviewed by Drugs.com. Last updated on April 15, 2019.

Introduction

Antibacterial; tetracycline anti-infective agent.1 2 4

Uses for Sarecycline

Acne Vulgaris

Treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris.1 2

Not evaluated for treatment of infections.1

Sarecycline Dosage and Administration

Administration

Oral Administration

Administer orally once daily with or without food.1

Take sarecycline tablets with adequate amounts of fluid to reduce risk of esophageal irritation and ulceration.1

Dosage

Available as sarecycline hydrochloride; dosage expressed in terms of sarecycline.1

Pediatric Patients

Acne Vulgaris
Oral

Pediatric patients ≥9 years of age with non-nodular moderate to severe acne vulgaris: Dosage is based on weight.1 (See Table 1.)

If no improvement after 12 weeks of treatment, reassess use of sarecycline.1 Efficacy for >12 weeks and safety for >12 months not established.1

Table 1: Sarecycline Dosage in Pediatric Patients ≥9 Years of Age 1

Body Weight (kg)

Dosage

33–54 kg

60-mg tablet once daily

55–84 kg

100-mg tablet once daily

85–136 kg

150-mg tablet once daily

Adults

Acne Vulgaris
Oral

Non-nodular moderate to severe acne vulgaris: Dosage is based on weight.1 (See Table 2.)

If no improvement after 12 weeks, reassess use of sarecycline.1 Efficacy for >12 weeks and safety for >12 months not established.1

Table 2: Sarecycline Dosage in Adults1

Body Weight (kg)

Dosage

33–54 kg

60-mg tablet once daily

55–84 kg

100-mg tablet once daily

85–136 kg

150-mg tablet once daily

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment (Child-Pugh class A or B): Dosage adjustments not needed.9

Severe hepatic impairment (Child-Pugh class C): Data not available.1

Renal Impairment

Mild, moderate, or severe renal impairment: Dosage adjustments not needed.9

End-stage renal disease: Data not available.1

Cautions for Sarecycline

Contraindications

  • Known hypersensitivity to any tetracycline.1

Warnings/Precautions

Sensitivity Reactions

Photosensitivity Reactions

Photosensitivity, manifested by an exaggerated sunburn reaction, reported in patients receiving tetracyclines.1

Minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) during sarecycline treatment.1 If patient needs to be outdoors, advise them to wear loose-fitting clothes that protect skin from sun exposure and to consider other sun protection measures.1

Dental and Bone Effects

Use of tetracyclines during tooth development (e.g., second and third trimesters of pregnancy, infancy, children ≤8 years of age) may cause permanent yellow-gray to brown discoloration of teeth and enamel hypoplasia.1 These dental effects are most common following long-term use of tetracyclines, but may occur following repeated short-term use.1

Tetracyclines form a stable calcium complex in any bone-forming tissue.1 Reversible decrease in fibula growth rate has occurred in premature infants given oral tetracycline in a dosage of 25 mg/kg every 6 hours.1

Fetal/Neonatal Morbidity

Animal studies indicate tetracyclines cross the placenta, are found in fetal tissue, and can cause fetal toxicity (e.g., retardation of skeletal development) and embryotoxicity.1

If sarecycline is used during pregnancy or if patient becomes pregnant while taking sarecycline, apprise patient of potential hazard to the fetus.1 (See Pregnancy under Cautions.)

CNS Effects

Adverse CNS effects (e.g., lightheadedness, dizziness, vertigo) reported with tetracyclines and may impair ability to drive vehicles or operate hazardous machinery.1 These symptoms may disappear during therapy or when drug discontinued.1

Intracranial hypertension reported in adults and adolescents receiving tetracyclines;1 usually manifested as headache, blurred vision, and papilledema.1 Although signs and symptoms usually resolve after the tetracycline discontinued, possibility exists that sequelae (e.g., visual loss) may be permanent or severe.1 Women of childbearing age who are overweight have a greater risk for developing intracranial hypertension.1

Because systemic retinoids also known to cause intracranial hypertension, do not use concomitantly with sarecycline.1 (See Specific Drugs under Interactions.)

Question patients about presence of visual disturbances prior to initiating a tetracycline.1 If visual disturbances occur during treatment, check for papilledema.1

Superinfection/Clostridium difficile-associated Colitis

Possible overgrowth of nonsusceptible organisms, including fungi.1 Discontinue sarecycline and institute appropriate therapy if superinfection occurs.1

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.1 6 7 8 C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all systemic anti-infectives and may range in severity from mild diarrhea to fatal colitis.1 6 7 8 C. difficile produces toxins A and B which contribute to development of CDAD;1 6 hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.1

Consider CDAD if diarrhea develops during or after anti-infective therapy.1 6 7 8 Obtain careful medical history since CDAD may occur as late as ≥2 months after anti-infective therapy discontinued.1

If CDAD suspected or confirmed, discontinue anti-infectives not directed against C. difficile whenever possible.1 8 Initiate anti-infective therapy directed against C. difficile (e.g., vancomycin, fidaxomicin, metronidazole), appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), and surgical evaluation as clinically indicated.1 6 7 8

Selection and Use of Anti-infectives

Use of sarecycline for treatment of acne vulgaris may result in emergence of bacteria resistant to tetracyclines.1

To reduce development of drug-resistant bacteria and maintain effectiveness of other antibacterials, use sarecycline only when indicated.1

Specific Populations

Pregnancy

Like other tetracyclines, may cause fetal harm, permanent discoloration of teeth, and reversible inhibition of bone growth if administered during pregnancy.1

Human data insufficient to inform a drug-associated risk for birth defects or miscarriage with sarecycline; consider that tetracyclines cross the placenta.1

If used during pregnancy or if patient becomes pregnant while taking sarecycline, apprise patient of potential hazard to the fetus.1

Because potential risks to the fetus outweigh potential benefits to the mother, discontinue sarecycline as soon as pregnancy recognized.1

Lactation

Tetracyclines are distributed into human milk.1 Advise women that breast-feeding is not recommended during sarecycline treatment.1

Fertility

Manufacturer states avoid use of sarecycline in males attempting to conceive a child.1

In animal fertility study, oral sarecycline adversely affected spermatogenesis (decreased sperm motility, decreased sperm count and concentration, increased percentage of abnormal sperm) in male rats;1 did not affect fertility in female rats.1

Pediatric Use

Safety and efficacy not established in pediatric patients <9 years of age.1

Safety and efficacy for treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris established in pediatric patients ≥9 years of age based on controlled clinical studies.1

Geriatric Use

Insufficient experience in geriatric patients ≥65 years of age to determine whether they respond differently than younger adults.1

Hepatic Impairment

Mild to moderate hepatic impairment (Child-Pugh class A or B): No clinically important effects on pharmacokinetics of sarecycline.1

Severe hepatic impairment (Child-Pugh class C): Effects on sarecycline pharmacokinetics not studied.1

Renal Impairment

Mild, moderate, or severe renal impairment: No clinically important effects on pharmacokinetics of sarecycline.1

End-stage renal disease: Effects on sarecycline pharmacokinetics not studied.1

Common Adverse Effects

Nausea.1

Interactions for Sarecycline

Does not inhibit CYP isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4/5 in vitro;1 does not induce CYP1A2, 2B6, or 3A4/5 in vitro.1

Minimally metabolized by hepatic microsomal enzymes.1

Inhibits P-glycoprotein (P-gp) in vitro;1 not a substrate of P-gp.1

Drugs Affected by P-glycoprotein Transport System

P-gp substrates: Possible increased concentrations of P-gp substrates.1 Monitor for toxicities associated with the P-gp substrate;1 may need to reduce dosage of the P-gp substrate.1

Specific Drugs

Drug

Interaction

Comments

Antacids (aluminum-, bismuth-, calcium-, or magnesium-containing)

Possible decreased sarecycline absorption and decreased efficacy1

Do not administer concomitantly1

Anticoagulants, oral

Sarecycline may depress plasma prothrombin activity and increase risk of bleeding in patients receiving anticoagulants1

Adjust anticoagulant dosage as needed1

Digoxin

Increased digoxin concentrations1

Monitor for digoxin toxicity;1 may need to reduce digoxin dosage1

Estrogens and progestins

Oral contraceptive containing ethinyl estradiol and norethindrone: Increased concentrations and AUC of ethinyl estradiol and norethindrone1

Oral contraceptive containing ethinyl estradiol and norethindrone: Interaction not considered clinically important1

Iron-containing preparations

May decrease sarecycline absorption and decrease efficacy1

Do not administer concomitantly1

Penicillins

Possible antagonistic antibacterial effects1

Avoid concomitant use1

Retinoids, systemic (acitretin, isotretinoin)

Oral retinoids may cause intracranial hypertension and increase intracranial pressure1

Avoid concomitant use with oral retinoids1

Sarecycline Pharmacokinetics

Absorption

Food

High-fat or high-caloric meal delays time to peak plasma concentrations by approximately 0.53 hours and decreases peak plasma concentrations and AUC by 31 and 27%, respectively.1 9 Not considered clinically important.9

Plasma Concentrations

Median time to peak plasma concentrations following oral administration: 1.5–2 hours.1

Once-daily oral administration: Steady-state reached by day 7.1

Distribution

Extent

Tetracyclines cross the placenta.1

Tetracyclines distributed into milk.1

Plasma Protein Binding

63–75%.1

Steady-state mean apparent volume of distribution: 91.4–97 L.1

Elimination

Metabolism

In vitro studies in human liver microsomes indicate minimal metabolism by hepatic enzymes (<15%).1

Minor metabolites resulting from nonenzymic epimerization, O/N-demethylation, hydroxylation, and desaturation identified.1

Elimination Route

After a single 100-mg oral dose, 43% recovered in feces (14.9% as unchanged drug) and 44% in urine (24.7% as unchanged drug).1

Half-life

Mean elimination half-life: 21–22 hours.1

Stability

Storage

Oral

Tablets

20°–25°C (may be exposed to 15–30°C).1 Protect from moisture and excessive heat.1

Actions and Spectrum

  • Tetracycline anti-infective;1 2 4 aminomethylcycline.4 10

  • Mechanisms of action in the treatment of acne vulgaris not known.1 May result from a combination of anti-infective and anti-inflammatory effects similar to that reported with other tetracyclines.4

  • Has a narrower spectrum of activity compared with other commercially available tetracyclines.4 Like other tetracyclines used in treatment of acne vulgaris (e.g., doxycycline, minocycline, tetracycline), sarecycline is active in vitro against Cutibacterium acnes (formerly Propionibacterium acnes), a gram-positive anaerobe that is a factor in the etiology of acne; however, sarecycline is less active in vitro than the other tetracyclines against enteric gram-negative bacteria or other anaerobic bacteria.4

Advice to Patients

  • Advise patients to read manufacturer’s patient information.1

  • Importance of drinking sufficient quantities of fluids when taking sarecycline tablets to reduce the risk of esophageal irritation and ulceration.1

  • Importance of taking as directed because of potential for development of drug-resistant bacteria.1 Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with other antibacterials in the future.1

  • Inform patients that photosensitivity manifested by an exaggerated sunburn reaction reported in some individuals taking tetracyclines.1 Advise patients to minimize or avoid sunlight or artificial UV light (e.g., tanning beds, UVA/B treatment) during sarecycline treatment and to discontinue the drug at first sign of skin erythema.1 If patient needs to be outdoors, advise them to wear loose-fitting clothes that protect skin from sun exposure and also consider other sun protection measures.1

  • Inform patients that intracranial hypertension can occur with tetracyclines.1 Importance of seeking medical attention if headache or blurred vision occurs.1

  • Advise patients to use caution when driving vehicles or using hazardous machinery if they experience CNS effects (lightheadedness, dizziness, vertigo) during sarecycline treatment.1 Importance of seeking medical attention if these CNS effects persist.1

  • Advise patients that C. difficile colitis can occur with anti-infective therapy.1 Importance of seeking medical attention if watery or bloody stools occur.1

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, and any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Advise patients that sarecycline should not be taken by pregnant women or by women or men attempting to conceive a child.1 (See Pregnancy and see Fertility under Cautions.) Advise women not to breast-feed during sarecycline treatment.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Sarecycline Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

60 mg (of sarecycline)

Seysara

Almirall

100 mg (of sarecycline)

Seysara

Almirall

150 mg (of sarecycline)

Seysara

Almirall

AHFS DI Essentials™. © Copyright 2021, Selected Revisions April 15, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Almirall, LLC. Seysara (sarecycline hydrochloride) tablets prescribing information. Exton, PA; 2018 Oct.

2. Moore A, Green LJ, Bruce S et al. Once-Daily Oral Sarecycline 1.5 mg/kg/day Is Effective for Moderate to Severe Acne Vulgaris: Results from Two Identically Designed, Phase 3, Randomized, Double-Blind Clinical Trials. J Drugs Dermatol. 2018; 17:987-996. http://www.ncbi.nlm.nih.gov/pubmed/30235387?dopt=AbstractPlus

3. Leyden JJ, Sniukiene V, Berk DR et al. Efficacy and Safety of Sarecycline, a Novel, Once-Daily, Narrow Spectrum Antibiotic for the Treatment of Moderate to Severe Facial Acne Vulgaris: Results of a Phase 2, Dose-Ranging Study. J Drugs Dermatol. 2018; 17:333-338. http://www.ncbi.nlm.nih.gov/pubmed/29537451?dopt=AbstractPlus

4. Zhanel G, Critchley I, Lin LY et al. Microbiological Profile of Sarecycline: A Novel Targeted Spectrum Tetracycline for the Treatment of Acne Vulgaris. Antimicrob Agents Chemother. 2018; http://www.ncbi.nlm.nih.gov/pubmed/30397052?dopt=AbstractPlus

5. Zaenglein AL, Pathy AL, Schlosser BJ et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016; 74:945-73.e33. http://www.ncbi.nlm.nih.gov/pubmed/26897386?dopt=AbstractPlus

6. McDonald LC, Gerding DN, Johnson S et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018; 66:987-994. http://www.ncbi.nlm.nih.gov/pubmed/29562266?dopt=AbstractPlus

7. Fekety R for the American College of Gastroenterology Practice parameters Committee. Guidelines for the diagnosis and management of Clostridium difficile-associated diarrhea and colitis. Am J Gastroenterol. 1997; 92:739-50. http://www.ncbi.nlm.nih.gov/pubmed/9149180?dopt=AbstractPlus

8. American Society of Health-System Pharmacists Commission on Therapeutics ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile-associated disease. Am J Health-Syst Pharm. 1998; 55:1407-11.

9. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 209521Orig1s000: Multi-discipline review. From FDA website. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209521Orig1s000MultidisciplineR.pdf

10. Almirall, LLC. Exton, Pa. Personal communication.

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