sarecycline (Rx)

1-10%

Nausea (3.1%)

<1%

Vulvovaginal mycotic infection

Vulvovaginal candidiasis

Contraindications

Hypersensitivity to any tetracyclines

Cautions

Clostridium difficile-associated diarrhea (CDAD) reported with use of nearly all antibacterial agents, and may range in severity from mild diarrhea to fatal colitis; if CDAD is suspected or confirmed, consider discontinuing ongoing antibacterial drug use not directed against C difficile and initiating treatment-appropriate measures

Central nervous system side effects including light-headedness, dizziness or vertigo reported with tetracycline use; patients who experience symptoms should be cautioned about driving vehicles or using hazardous machinery; symptoms may disappear during therapy and may disappear when drug is discontinued

Photosensitivity manifested by an exaggerated sunburn reaction observed with tetracyclines; instruct patients to minimize or avoid exposure to natural or artificial sunlight; if patients need to be outdoors while on therapy, they should wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician

Bacterial resistance to tetracyclines may develop; because of this, use only as indicated

As with other antibiotics, use may result in overgrowth of nonsusceptible organisms, including fungi; if superinfection occurs, discontinue therapy and institute appropriate therapy

Intracranial hypertension

• Intracranial hypertension in adults and adolescents associated with tetracycline use; clinical manifestations include headache, blurred vision, and papilledema; if visual disturbance occurs during treatment, patients should be checked for papilledema
• 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 should be avoided because isotretinoin, a systemic retinoid, is also known to cause intracranial hypertension

Teratogenic effects

• Can cause fetal harm if used during pregnancy

• Use during tooth and bone development

  • Use during tooth development (last half of pregnancy, infancy, and childhood to age 8 years) may cause permanent discoloration of the teeth (yellow-grey-brown); enamel hypoplasia reported with tetracyclines; advise patient of potential risk
  • May cause reversible inhibition of bone growth during pregnancy, infancy, and early childhood
  • All tetracyclines form a stable calcium complex in any bone-forming tissue
  • Decreased fibula growth rate observed in premature infants given PO tetracycline in doses of 25 mg/kg q6hr; reversible when drug discontinued
  • Also see Pregnancy

Drug interaction overview

• Avoid coadministration with oral retinoids; may have additive effects on increasing intracranial pressure
• Coadministration with antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate, and iron-containing preparations decrease tetracycline absorption, which may decrease efficacy; separate doses
• May interfere with bacteriocidal action of penicillin; avoid coadministration
• May depress plasma prothrombin activity, which may increase bleeding risk in patients who are on anticoagulant therapy
• May increase serum concentration of P-gp substrates; monitor for toxicities if P-gp substrates coadministered

Pregnancy

Like other tetracycline-class antibacterial drugs, may cause discoloration of deciduous teeth and reversible inhibition of bone growth when administered during second and third trimesters of pregnancy

Pregnant women should discontinue sarecycline as soon as pregnancy is recognized

Animal data

• Crosses placenta and is found in fetal plasma; sarecycline induced skeletal malformations in fetuses when administered PO 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)

Infertility

• Based on animal studies, can lead to impaired spermiation and sperm maturation, resulting in abnormal sperm morphology and poor motility
• Avoid use in males who are attempting to conceive a child

Lactation

Tetracyclines are excreted in human milk

Because of the potential for serious adverse reactions on bone and tooth development in nursing infants, sarecycline is not recommended in breastfeeding women

Animal studies

• 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

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Tetracycline-derived antibiotic; narrow spectrum of activity targeting acne-specific pathogens (ie, Propionibacterium acnes, Staphylococcus aureus)

Elicits limited activity against aerobic gram-negative gastrointestinal organisms compared with minocycline and doxycycline

Absorption

Peak plasma time: 1.5-2 hr

Effect of high-fat and high-calorie meal

• Peak plasma time: Delayed by ~0.53 hr
• Peak plasma concentration: Decreased by 31%
• AUC: Decreased by 27%

Distribution

Protein bound: 62.5-74.7%

Vd: 91.4-97 L

Metabolism

Minimal hepatic metabolism (<15%)

Minor metabolites resulting from nonenzymic epimerization, O-/N-demethylation, hydroxylation, and desaturation found

Elimination

Half-life: 21-22 hr

Clearance: 3 L/hr

Excretion: 42.6% feces (14.9% unchanged); 44.1% urine (24.7% unchanged)

Oral Administration

Take with or without food

Swallow with adequate amounts of fluid to reduce risk of esophageal irritation or ulceration

Storage

Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)

Protect from moisture and excessive heat