FDA Approves NUZYRA (Omadacycline) for Community-Acquired Bacterial Pneumonia and for Acute Bacterial Skin and Skin Structure Infections in Adults

FDA Approves NUZYRA (Omadacycline) for Community-Acquired Bacterial Pneumonia and for Acute Bacterial Skin and Skin Structure Infections in Adults

On October 2, 2018, the U.S. Food and Drug Administration (FDA) approved NUZYRA (omadacycline) for the treatment of adult’s patients with the following infections caused by susceptible microorganisms:

• Community-acquired bacterial pneumonia (CABP)
• Acute bacterial skin and skin structure infections (ABSSSI)

To reduce the development of drug-resistant bacteria and maintain the effectiveness of NUZYRA and other antibacterial drugs, NUZYRA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.  The approved recommended dosage of NUZYRA for CABP and ABSSSI is shown below: 

• CABP: Loading dose on day 1 is 200 mg by intravenous (IV) infusion over 60 minutes OR 100 mg by IV infusion over 30 minutes twice.  NUZYRA maintenance dosage for CABP is 100 mg by IV infusion over 30 minutes once daily OR 300 mg orally once daily.  
• ABSSSI: Loading dose on day 1 is 200 mg by IV infusion over 60 minutes OR 100 mg by IV infusion over 30 minutes twice.  NUZYRA maintenance dosage for ABSSSI is 100 mg by IV infusion over 30 minutes once daily OR 300 mg orally once daily. 
• ABSSSI (tablets only): Loading dose on day 1 and day 2 is 450 mg orally once daily and the maintenance dosage is 300 mg orally once daily. 

NUZYRA treatment duration for CABP and ABSSSI is 7 to 14 days.

When administering NUZYRA tablets ensure that the patient fasts for at least 4 hours and then takes NUZYRA tablets with water.  After oral dosing, no food or drink (except water) is to be consumed for 2 hours and no dairy products, antacids, or multivitamins for 4 hours. Do NOT administer NUZYRA for injection with any solution containing multivalent cations, e.g., calcium and magnesium, through the same intravenous. Co-infusion with other medications has not been studied. 

Closely monitor clinical response to therapy in CABP patients, particularly in those at higher risk for mortality. The use of NUZYRA may cause permanent discoloration of the teeth and enamel hypoplasia, inhibition of bone growth, and clostridium difficile-associated diarrhea.

Additional information regarding dosage and administration and important warnings and precautions, including a mortality imbalance, can be found in the full prescribing information linked below.

Mechanism of Action (MOA) and Pharmacokinetics (PK)

• MOA: NUZYRA is a tetracycline class antibacterial drug.
• General PK:  Following single oral doses of NUZYRA 300 to 450 mg in healthy subjects resulted in dose proportional increases in omadacycline C_max and AUC.  The mean accumulation ratio of NUZYRA was 1.5.
• Absorption: The bioavailability is 34.5% following a single 300 mg dose of NUZYRA.  The median T_max of NUZYRA for 100 mg IV dose is 0.55 hour and for 300 mg and 450 mg oral doses is 2.5 hours.
• Distribution: Protein binding of omadacycline is 20% and is not concentration dependent.  The mean (%CV) volume of distribution of omadacycline at steady state following IV administration of NUZYRA 100 mg was 190 (27.7) L.  
• Elimination: The mean elimination half-life of omadacycline at steady state is 16, 15.5, and 16.83 hours for NUZYRA 100 mg IV, 300 mg oral and 450 mg oral dosages, respectively.  
• Metabolism: In vitro studies using human liver microsomes and hepatocytes demonstrated that omadacycline is not metabolized.  
• Excretion: Following a 100 mg IV dose of NUZYRA, 27% of the dose was recovered as unchanged omadacycline in the urine.  In healthy male volunteers receiving 300 mg oral radiolabeled omadacycline, 77.5% to 84% of the dose was recovered in the feces, approximately 14.4% (range 10.8% to 17.4%) in the urine, with 95.5% of the administered dose recovered after 7 days.
• Lactation: Breastfeeding is not recommended during treatment in NUZYRA and for 4 days (based on half-life) after the last dose.

Drug Interactions

• Anticoagulant Drugs: Tetracyclines have shown to depress plasma prothrombin activity. Patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage while also taking NUZYRA.
• Antacids and Iron Preparations: Absorption of oral tetracyclines, including NUZYRA, is impaired by antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate, and iron containing preparations. 

Use in Specific Populations

No clinically significant differences in the pharmacokinetics of omadacycline were observed based on age, sex, race/ethnicity, weight, renal impairment, end-stage renal disease, or hepatic impairment. 

 

Efficacy and Safety

Efficacy of NUZYRA was demonstrated in a multinational, double-blind, double-dummy trial comparing NUZYRA to moxifloxacin in adults with CABP.  Efficacy of NUZYRA was demonstrated in two multicenter, multinational, double-blind, double dummy trials in adults with ABSSSI which compared NUZYRA to linezolid.  The ABSSSI trials enrolled patients with cellulitis, major abscess, or wound infection.  Additional information regarding efficacy trial(s) can be found in the full prescribing information linked below.

Most common adverse reactions (incidence ≥ 2%) includes nausea, vomiting, infusion site reactions, alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyl transferase increased, hypertension, headache, diarrhea, insomnia, and constipation. 

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Full prescribing information is available at https://go.usa.gov/xPku9. 

Visit Drugs@FDA at http://go.usa.gov/cMsjT for prescribing and patient information, approval letters, reviews and other information for FDA-approved drug products, which are often available shortly following approval. 

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online athttp://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178), or by mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.