Omadacycline Injection and Tablets (Nuzyra)
December 30, 2018
By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved a broad-spectrum antibiotic for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSI). Omadacycline is a semisynthetic derivative of tetracycline (aminomethycycline) but is active against traditional tetracycline-resistant bacteria. Omadacycline, given a priority review, will be distributed in injectable and oral forms as Nuzyra.
INDICATIONS
Omadacycline is indicated for the treatment of adults with CABP caused by the following susceptible microorganisms: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.1 Omadacycline also is indicated for ABSSSI caused by the following susceptible microorganisms: S. aureus (methicillin-susceptible and -resistant isolates), Staphylococcus lugdunensis, Streptococcus pyogenes, Streptococcus anginosus group (including S. anginosus, S. intermedius, and S. constellatus), Enterococcus faecalis, Enterococcus cloacae, and Klebsiella pneumoniae.1
DOSAGE
For CABP, the loading dose is 200 mg by IV infusion once or 100 mg twice (every 12 hours) on day 1.1 The maintenance dose is 100 mg by infusion daily or 300 mg orally once daily for seven to 14 days. For ABSSSI, the loading and maintenance doses are the same as for CABP. For oral administration only, the dose is 450 mg once daily on days 1 and 2, followed by 300 mg once daily for seven to 14 days. High-fat meals (both dairy and nondairy) reduce the absorption of omadacycline; therefore, a four-hour fast is recommended before taking the tablet and no food or drinks should be consumed for two hours after taking omadacycline. In addition, no dairy products, antacids, or multivitamins should be consumed for four hours after taking oral omadacycline.
POTENTIAL ADVANTAGES
Omadacycline has shown in vitro activity against bacteria carrying resistant genes to tetracycline and some carrying macrolide- and ciprofloxacin-resistant genes.1,2 It is active against methicillin-resistant S. aureus (MRSA) and penicillin- and macrolide-resistant S. pneumoniae isolates.2 Both the injectable and oral forms can be given once daily.
POTENTIAL DISADVANTAGES
Food restriction due to food-drug interaction with the oral formulation may cause compliance problems. Using omadacycline during pregnancy may cause permanent discoloration of teeth, enamel hypoplasia, and reversible inhibition of bone growth in the child.1 Because of the structural similarity to tetracycline, omadacycline may share adverse reactions such as photosensitivity, pseudotumor cerebri, and anti-anabolic actions.1 Generally, omadacycline is bacteriostatic but may be bactericidal against some isolates of S. pneumoniae and H. influenzae.1 The most frequently reported adverse reactions (> 5%) were nausea (22%), vomiting (11%), and infusion site reactions (5.2%).1
COMMENTS
Researchers compared the safety and efficacy of omadacycline compared to moxifloxacin in adults with CABP in a randomized, double-blind, noninferiority study.1,3 Sixty percent had pneumonia with severity index (PORT Risk) class III and 26% had class IV. Subjects were randomized to omadacycline 100 mg injectable every 12 hours for two doses, followed by 100 mg injectable or 300 mg orally daily (n = 386), or moxifloxacin 400 mg injectable or orally daily (n = 388). The total treatment duration was seven to 14 days. Clinical success was assessed 72-120 hours after the first dose (early clinical response [ECR]) and five to 10 days after the last day of therapy (post-treatment response ([PTR]). Clinical success was defined as survival with improvement of at least one point from baseline on a four-point scale.4 Symptoms included the frequency and severity of cough, sputum production, pleuritic chest pain, and dyspnea. ECR rates were 81.1% for omadacycline and 82.7% for moxifloxacin. PTR rates were 87.6% and 85.1%, respectively. The most common baseline pathogens were S. pneumoniae, M. pneumoniae, H. influenzae, and L. pneumophilia. For ABSSSI, omadacycline was evaluated in two randomized, noninferiority studies in patients with infections such as cellulitis, major abscess, or wound infections with a mean infected surface area of 399-498 cm2.1,5,6 In study 1, subjects were randomized to 100 mg injectable omadacycline for two doses then 100 mg injectable every 24 hours, with the option to switch to 300 mg orally every 24 hours or 600 mg injectable linezolid every 12 hours and the option to switch to 600 mg orally every 12 hours. In study 2, subjects were randomized to oral omadacycline 450 mg once daily on days 1 and 2, followed by 300 mg daily or oral linezolid 600 mg every 12 hours. ECR was assessed 48-72 hours after the first dose and PTR seven to 14 days after the last dose. Success was determined as survival with ≥ 20% reduction in lesion size.7 ECR rates were 84.8% for omadacycline and 85.5% for linezolid in study 1 and 87.3% vs. 82.2% in study 2, respectively. Corresponding rates for PTR were 86.1% vs. 83.6% in study 1 and 83.9% vs. 80.5% for study 2. The most common baseline pathogen was S. aureus, with about 45% MRSA.
CLINICAL IMPLICATIONS
Omadacycline was found to be noninferior to moxifloxacin in CABP and linezolid in ABSSSI. In both instances, the comparators were considered one of the first-line agents for CABP and ABSSSI involving MRSA.8,9 The drug appears to be active against MRSA, drug-resistant S. pneumoniae, and erythromycin-resistant Group A Streptococcus, organisms that the CDC considers serious or concerning threats.10
Omadacycline is a potential new option for CABP and ABSSI caused by these drug-resistant strains of bacteria. Omadacycline should be used only to treat infections caused by bacteria that are proven or strongly suspected to be caused by susceptible bacteria. Omadacycline is expected to be available in the first quarter of 2019.
REFERENCES
- Nuzyra Prescribing Information. Paratek Pharmaceuticals, Inc., October 2018. Available at: https://bit.ly/2Ok9zXF. Accessed Dec. 7, 2018.
- Pfaller MA, et al. Surveillance of omadacycline activity tested against clinical isolates from the United States and Europe as part of the 2016 SENTRY Antimicrobial Surveillance Program. Antimicrob Agents Chemother 2018;62. pii: e02327-17.
- ClinicalTrials.gov. Omadacycline vs moxifloxacin for the treatment of CABP (EudraCT #2013-004071-13). Available at: https://bit.ly/2PpuxVC. Accessed Dec. 7, 2018.
- U.S. Food and Drug Administration. Guidance for Industry Community-Acquired Bacterial Pneumonia: Developing Drugs for Treatment, Draft Guidance. January 2014. Available at: https://bit.ly/2Ei97Zz. Accessed Dec. 7, 2018.
- ClinicalTrials.gov. Omadacycline versus linezolid for the treatment of ABSSSI (EudraCT #2013-003644-23). Available at: https://bit.ly/2QiYNae. Accessed Dec. 7, 2018.
- ClinicalTrials.gov. Oral omadacycline vs. oral linezolid for the treatment of ABSSSI. Available at: https://bit.ly/2B2Q8y7. Accessed Dec. 7, 2018.
- U.S. Food and Drug Administration. Guidance for Industry. Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for Treatment. October 2013. Available at: https://bit.ly/2tDArfU. Accessed Dec. 7, 2018.
- Mandell LA, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44 (Suppl 2)S27-S72.
- Stevens DL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014;59:e10-52.
- Centers for Disease Control and Prevention. Antibiotic/Antimicrobial Resistance, Biggest Threats and Data. Available at: https://bit.ly/29286mX. Accessed Dec. 7, 2018.
The FDA has approved a broad-spectrum antibiotic for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections.
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