Omadacycline

Indications

Omadacycline is used for: Community-Acquired Bacterial Pneumonia, Bacterial Skin and Skin Structure Infections

Adult Dose

Community-Acquired Bacterial Pneumonia Indicated for treatment of community-acquired bacterial pneumonia (CABP) caused by susceptible microorganisms Loading dose (Day 1): 200 mg IV once OR 100 mg IV x 2 doses Maintenance dose: 100 mg IV qDay OR 300 mg PO qDay Treatment duration: 7-14 days Bacterial Skin and Skin Structure Infections Indicated for treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by susceptible microorganisms Treatment duration: 7-14 days Loading dose IV (Day 1): 200 mg IV once OR 100 mg IV x 2 doses OR PO (Days 1 and 2): 450 mg PO qDay x 2 days Maintenance dose IV: 100 mg IV qDay OR PO: 300 mg PO qDay

Child Dose

<18 years: Safety and efficacy not established

Renal Dose

Renal or hepatic impairment No dosage adjustment required with any severity of renal or hepatic impairment, including patients with ESRD or those receiving dialysis

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 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

Contra Indications

Hypersensitivity to any tetracyclines

Precautions

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

Pregnancy-Lactation

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

Interactions

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

Side Effects

Side effects of Omadacycline :

Mode 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