omadacycline (Rx)

Tetracycline class effects

• Intracranial hypertension, pseudotumor cerebri, antianabolic action reported in adults and adolescents associated with tetracycline use; clinical manifestations include headache, blurred vision, and papilledema
• Photosensitivity manifested by an exaggerated sunburn reaction observed with tetracyclines; instruct patients to minimize or avoid exposure to natural or artificial sunlight
• Increased BUN, azotemia, acidosis, hyperphosphatemia, pancreatitis, and abnormal liver function tests may occur
• Discontinue if these adverse effects suspected

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

Animal data

• Administration during organogenesis resulted in fetal loss and/or congenital malformations in pregnant rats and rabbits at 7 times and 3 times the mean AUC exposure, respectively, of the clinical IV dose of 100 mg and the oral dose of 300 mg; reductions in fetal weight occurred in rats at all administered doses

Infertility

• Males: Based on animal studies, can lead to impaired spermiation and sperm maturation, resulting in abnormal sperm morphology and poor motility
• Females: Based on animal studies, omadacycline affected fertility parameters, resulting in reduced ovulation and increased embryonic loss at intended human exposures

Contraception

• Advise women of reproductive potential to use highly effective form of contraception

Excretion

• Urine
  • IV: 27%
  • PO: 14.4%
• Feces
  • PO: 81.1%

Reconstitution

• Calculate dose and number of vials needed
• Reconstitute each 100-mg vial with 5 mL of sterile water for injection
• Do not shake; gently swirl vial contents and let stand until the lyophilized cake has completely dissolved and any foam disperses
• Reconstituted solution should appear yellow to dark orange; if not, discard solution
• Visually inspect for particulate matter and discoloration before further dilution and administration; if needed, invert vial to dissolve any remaining powder and swirl gently to prevent foaming

Dilution

• Within 1 hr of reconstitution, withdraw solution from vial(s) and further dilute by adding to 100-mL bag of 0.9% NaCl or D5W
• If diluted infusion bag is refrigerated, remove from refrigeration, place in upright vertical position, and allow bag to come to room temperature 60 minutes before use

Vials of lyophilized power or tablets

• Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)
• Do not freeze

Diluted IV solution

• Room temperature: Use within 24 hr when stored at ≤77°F (≤25°C)
• Refrigerated: Use within 48 hr when refrigerated 36-46°F (2-8°C); do not freeze