omadacycline (Rx)

>10% (ABSSSI)

Nausea (21.9%)

Vomiting (11.4%)

1-10% (ABSSI)

Infusion site reactions (5.2%)

Increased ALT (4.1%)

Increased AST (3.6%)

Headache (3.3%)

Diarrhea (3.2%)

1-10% (CABP)

Increased ALT (3.7%)

Hypertension (3.4%)

Increased GGT (2.6%)

Insomnia (2.6%)

Vomiting (2.6%)

Constipation (2.4%)

Nausea (2.4%)

Increased AST (2.1%)

Headache (2.1%)

Contraindications

Hypersensitivity to any tetracyclines

Cautions

Mortality imbalance observed in the CABP clinical trial, with 8 deaths (2%) occurring in patients treated with omadacycline compared with 4 deaths (1%) in patients treated with moxifloxacin; cause not established; all deaths, in both treatment arms, occurred in patients aged >65 years and most patients had multiple comorbidities

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

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

Hypersensitivity reactions reported; life-threatening hypersensitivity (anaphylactic) reactions reported with other tetracyclines (see Contraindications)

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

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 omadacycline as soon as pregnancy is recognized

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

Lactation

Tetracyclines are excreted in human milk

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

Advise women not to breastfeed during treatment and for 4 days after last dose

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

Aminomethylcycline antibacterial within the tetracycline drug class

Binds to the 30S ribosomal subunit and blocks protein synthesis

Active in vitro against gram-positive bacteria expressing tetracycline resistance active efflux pumps (tetK and tet L) and ribosomal protection proteins (tet M)

In general, considered bacteriostatic; however, has demonstrated bactericidal activity against some isolates of S pneumoniae and H influenzae

Absorption

Bioavailability: 34.5% (single 300-mg dose)

Peak plasma time, steady-state: 0.5 hr (IV); 2.5 hr (PO)

Peak plasma concentration, steady-state: 2120 ng/mL (IV); 952-1077 ng/mL (PO)

AUC, steady-state: 12,140 hr·ng/mL (IV); 11,156-13,367 hr·ng/mL (PO)

Distribution

Protein bound: 20%

Vd, steady-state: 190 L (IV)

Metabolism

Not metabolized

Elimination

Half-life, steady-state: 16 hr (IV); 15.5-16.8 hr (PO)

Systemic clearance, steady-state: 8.8 L/hr (IV)

Renal clearance: 2.4-3.3 L/hr

Excretion

• Urine

  • IV: 27%
  • PO: 14.4%

• Feces

  • PO: 81.1%

Oral Administration

Instruct patients not to eat or drink (other than water) 4 hr before or 2 hr after taking omadacycline tablets

Do not to consume dairy products, antacids, or multivitamins for 4 hr after taking tablets

IV Compatibilities

0.9% NaCl

D5W

IV Preparation

Lyophilized powder must be reconstituted and then further diluted

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

IV Administration

Infuse through dedicated IV line or Y-site

If same IV line is used for sequential infusion of several drugs, flush with 0.9% NaCl or D5W before and after omadacycline

100-mg dose: Infuse over 30 minutes

200-mg dose: infuse over 60 minutes

Storage

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