Prescribing Information

For US Healthcare Professionals only

Clinical Data

Early and sustained clinical response1

Primary endpoint

The majority of patients showed an early clinical response at 2 to 3 days after initiation of therapy1

Secondary endpoint

In mITT-PTE population, clinical cure* achieved with once-daily dosing1

Secondary endpoint

In CE-PTE population, clinical cure* achieved with once-daily dosing1

* Clinical cure at the post-treatment evaluation was defined as survival after completion of study treatment without receiving any other antibacterial therapy or unplanned major surgical intervention, and having sufficient resolution of infection such that further antibacterial therapy is not needed.1

Secondary endpoint

Reduced lesion size within days2,3†‡

†mITT population was defined as all randomized patients without a sole gram-negative causative pathogen at screening. ‡Minimum lesion size to qualify for inclusion in both studies was 75 cm2.
See full ABSSSI clinical trials study designs1

OASIS-2, known as Trial 3 in the NUZYRA Prescribing Information, was a randomized, multicenter, multinational, US-based, double-blind, double-dummy trial comparing the noninferiority of NUZYRA in patients with wound infection, cellulitis, and major abscess. NUZYRA was administered in a 450-mg oral dose once a day on Days 1 and 2, followed by 300 mg orally once a day. Patients were treated for 7 to 14 days.1

OASIS-1, known as Trial 2 in the NUZYRA Prescribing Information, was a randomized, multicenter, multinational, double-blind, double-dummy trial comparing the noninferiority of NUZYRA to linezolid. Types of infections included wound infection, cellulitis, and major abscess. NUZYRA was administered in 100-mg doses intravenously every 12 hours for 2 doses followed by 100-mg doses intravenously every 24 hours, with the option to switch to 300 mg orally every 24 hours. Linezolid was administered in 600-mg doses intravenously every 12 hours, with the option to switch to 600 mg orally every 12 hours. Patients were treated for 7 to 14 days.1

Endpoints1

  • Primary endpoint at ECR (early clinical response, 48 to 72 hours post-initiation of treatment) in the mITT population was defined as a ≥20% decrease in lesion size, without receiving any rescue antibacterial therapy§
  • Secondary endpoint at PTE (7 to 14 days after last dose) was defined as survival after completion of study treatment without receiving any other antibacterial therapy or unplanned major surgical intervention, and having sufficient resolution of infection such that further antibacterial therapy is not needed, and the infection was considered clinically cured. The secondary endpoint was evaluated in the mITT and in the CE populations1
  • Modified intent-to-treat (mITT) population was defined as all randomized patients without a sole gram-negative causative pathogen at screening due to the lack of gram-negative activity of linezolid
  • Clinically evaluable (CE) population was defined as mITT patients who met inclusion criteria and completed the trial, with a post-therapy evaluation (PTE) visit 7 to 14 days after the last dose
  • Microbiological mITT (micro-mITT) population was defined as all patients in the mITT population who had at least 1 gram-positive causative pathogen identified at baseline

§Reasons for failure included <20% reduction in lesion size, administration of rescue antibacterial therapy, use of another antibacterial or surgical procedure to treat for lack of efficacy, or death.1

CI=confidence interval; MRSA=methicillin-resistant Staphylococcus aureus.

Post-hoc analyses

Clinical cure results in patients with common comorbidities4,5

Post-hoc analysis study design and limitations4,5

These data are from a secondary post-hoc analysis of pooled subpopulations of patients with comorbidities from OASIS-1 and OASIS-2. Subpopulations were defined as: healthy weight (BMI 18.5 kg/m2 to <25 kg/m2), overweight (BMI 25 kg/m2 to <30 kg/m2), and obese (BMI ≥30 kg/m2); normal renal function (CrCl >89 mL/min), mild renal impairment (CrCl 60–89 mL/min), and moderate renal impairment (CrCl <60 mL/min); and patients with and without a history of diabetes.

Limitations of this analysis:

  • The exploratory nature of these post-hoc analyses, pooling of data from studies with different treatment regimens, and small sample sizes in some subgroups limit any conclusions from being drawn
  • Analyses were not powered to determine statistical significance. Data should not be interpreted as providing evidence of either superiority or noninferiority in these subgroups
  • The OASIS studies excluded patients with unstable cardiovascular disease, or clinically significant liver or renal insufficiency

BMI=body mass index; CABP=community-acquired bacterial pneumonia; CE-PTE=clinically evaluable post-therapy evaluation; CI=confidence interval; CrCl=creatinine clearance; mITT-PTE=modified intent-to-treat post-therapy evaluation; MRSA=methicillin-resistant Staphylococcus aureus.

Safety results from OASIS-1 and OASIS-2

Adverse reactions (ARs) occurring in ≥2% of patients: pooled OASIS-1 and OASIS-2 trials1

ADVERSE REACTION NUZYRA (N=691) LINEZOLID (N=689)
Nauseaa 22% 9%
Vomitinga 11% 4%
Infusion site reactionsb 5% 4%
Alanine aminotransferase increased 4% 4%
Aspartate aminotransferase increased 4% 4%
Headache 3% 3%
Diarrheac 3% 3%

Serious ARs and ARs leading to discontinuation1

  • Serious ARs occurred in 16/691 (2.3%) patients treated with NUZYRA and 13/689 (1.9%) patients treated with linezolid
  • 12 (1.7%) NUZYRA-treated patients and 10 (1.5%) linezolid-treated patients discontinued treatment due to ARs
  • There was 1 death reported in NUZYRA-treated patients and 3 deaths reported in linezolid-treated patients

In OASIS-1, which included IV to oral dosing of NUZYRA, 40 (12%) patients experienced nausea and 17 (5%) patients experienced vomiting in the NUZYRA treatment group compared to 32 (10%) patients who experienced nausea and 16 (5%) patients who experienced vomiting in the comparator group. One patient (0.3%) in the NUZYRA group discontinued treatment due to nausea and vomiting. In OASIS-2, which included the oral loading dose of NUZYRA, 111 (30%) patients experienced nausea and 62 (17%) patients experienced vomiting in the NUZYRA treatment group compared to 28 (8%) patients who experienced nausea and 11 (3%) patients who experienced vomiting in the linezolid group. Nausea in patients taking NUZYRA oral-only was mild to moderate and mostly limited to Day 1 or Day 2.4 One patient (0.3%) in the NUZYRA group discontinued treatment due to nausea and vomiting.1

aOnset of nausea and vomiting occurred primarily during the loading dose period on Day 1 and Day 2 in 25.3% and 12.5% of patients receiving NUZYRA. After Day 2, onset of nausea and vomiting occurred in 4.9% and 4.3% of NUZYRA patients.2 bInfusion site extravasation, pain, erythema, swelling, inflammation, irritation, peripheral swelling, and skin induration.1 cNo reports of Clostridioides difficile infection in either treatment group.4,5

Primary endpoint

Early clinical response at 3 to 5 days after initiation of IV therapy1,6

OPTIC

ITT population

NUZYRA
(n=313/386)

MOXIFLOXACIN
(n=321/398)

Difference: 95% CI, -1.6 (-7.1, 3.8)

Secondary endpoint

Consistent and effective results 5 to 10 days after last dose1

ITT-PTE population

NUZYRA
(n=338/386)

MOXIFLOXACIN
(n=330/388)

Difference: 95% CI, 2.5 (-2.4, 7.4)

CE-PTE population

NUZYRA
(n=316/343)

MOXIFLOXACIN
(n=312/345)

Difference: 95% CI, +2.5 (-1.7, 6.8)

See full CABP clinical trial study design

Study design1,6:

OPTIC was a phase 3, multinational, double-blind, double-dummy, noninferiority clinical trial. 774 adults with CABP were randomized 1:1. NUZYRA was administered 100 mg intravenously every 12 hours for 2 doses on Day 1, followed by 100 mg intravenously daily, or 300 mg orally, daily. Moxifloxacin 400 mg was administered intravenously or orally daily. Total treatment duration was 7 to 14 days. All enrolled patients were expected to require a minimum of at least 3 days of intravenous treatment.

Endpoints1:

  • Primary endpoint at ECR (early clinical response, 72 to 120 hours after the first dose) was defined as survival with improvement in ≥2 of 4 symptoms (cough, sputum production, chest pain, dyspnea) without deterioration in any of these 4 symptoms, and without receiving rescue antibacterial treatment. The primary endpoint was evaluated in the ITT population. End of treatment was between 7 to 14 days
  • Secondary endpoint at PTE (post-therapy evaluation, 5 to 10 days after last dose) was defined as survival and improvement in signs and symptoms of CABP, based on the clinician’s judgment, to the extent that further antibacterial therapy is not necessary, and the infection was considered clinically cured. The secondary endpoint was evaluated in the ITT and in the CE populations1,6
  • Intent-to-treat (ITT) population was defined as all randomized patients
  • Clinically evaluable (CE) population was defined as all ITT patients who met inclusion criteria and completed the trial

Post-hoc analyses

Clinical cure* results in patients with common comorbidities4,7,8

Limitations of these analyses:

  • The exploratory nature of these post-hoc analyses and small sample sizes in some subgroups limit any conclusions from being drawn
  • Analyses were not powered to determine statistical significance. Data should not be interpreted as providing evidence of either superiority or noninferiority in these subgroups
  • The OPTIC Study excluded patients with unstable cardiovascular disease, clinically significant liver or renal insufficiency, or severe COPD

*Clinical cure at the post-therapy evaluation (PTE) was defined as survival after completion of study treatment without receiving any other antibacterial therapy or unplanned major surgical intervention, and having sufficient resolution of infection such that further antibacterial therapy is not needed.1

BMI=body mass index; COPD=chronic obstructive pulmonary disease; CrCl=creatinine clearance.

Safety results from OPTIC Trial

Adverse reactions (ARs) occurring in ≥2% of patients in OPTIC1

ADVERSE REACTION NUZYRA (N=382) MOXIFLOXACIN (N=388)
Alanine aminotransferase increased 3.7% 4.6%
Hypertension 3.4% 2.8%
Gamma-glutamyl transferase increased 2.6% 2.1%
Insomnia 2.6% 2.1%
Vomiting 2.6% 1.5%
Constipation 2.4% 1.5%
Nausea 2.4% 5.4%
Aspartate aminotransferase increased 2.1% 3.6%
Headache 2.1% 1.3%

Serious ARs and ARs leading to discontinuation1

  • 23 (6.0%) patients treated with NUZYRA vs 26 (6.7%) treated with moxifloxacin experienced serious ARs
  • 21 (5.5%) patients treated with NUZYRA vs 27 (7.0%) treated with moxifloxacin discontinued treatment due to any ARs

In OPTIC, also known as Trial 1, 4 (1%) patients experienced diarrhea in the NUZYRA treatment group as compared to 31 (8%) patients in the moxifloxacin group. No case of Clostridioides difficile infection (Clostridioides difficile infection, Clostridioides difficile colitis, or pseudomembranous colitis) were reported in patients taking NUZYRA, compared to 8 (2.1%) moxifloxacin patients.6

IMPORTANT SAFETY INFORMATION

INDICATIONS and USAGE

NUZYRA® (omadacycline) is a tetracycline-class antibacterial indicated for the treatment of adult patients with the following infections caused by susceptible microorganisms:

Community-Acquired Bacterial Pneumonia (CABP) caused by the following: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.

Acute Bacterial Skin and Skin Structure Infections (ABSSSI) caused by the following: Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Staphylococcus lugdunensis, Streptococcus pyogenes, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Enterococcus faecalis, Enterobacter cloacae, and Klebsiella pneumoniae.

USAGE

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.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

NUZYRA is contraindicated in patients with known hypersensitivity to omadacycline or tetracycline-class antibacterial drugs, or to any of the excipients.

WARNINGS AND PRECAUTIONS

Mortality imbalance was observed in the CABP clinical trial with eight deaths (2%) occurring in patients treated with NUZYRA compared to four deaths (1%) in patients treated with moxifloxacin. The cause of the mortality imbalance has not been established. All deaths, in both treatment arms, occurred in patients >65 years of age; most patients had multiple comorbidities. The causes of death varied and included worsening and/or complications of infection and underlying conditions. Closely monitor clinical response to therapy in CABP patients, particularly in those at higher risk for mortality.

The use of NUZYRA during tooth development (last half of pregnancy, infancy and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown) and enamel hypoplasia.

The use of NUZYRA during the second and third trimester of pregnancy, infancy and childhood up to the age of 8 years may cause reversible inhibition of bone growth.

Hypersensitivity reactions have been reported with NUZYRA. Life-threatening hypersensitivity (anaphylactic) reactions have been reported with other tetracycline-class antibacterial drugs. NUZYRA is structurally similar to other tetracycline-class antibacterial drugs and is contraindicated in patients with known hypersensitivity to tetracycline-class antibacterial drugs. Discontinue NUZYRA if an allergic reaction occurs.

Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs.

NUZYRA is structurally similar to tetracycline-class antibacterial drugs and may have similar adverse reactions. Adverse reactions, including photosensitivity, fixed drug eruption, pseudotumor cerebri, and anti-anabolic action (which has led to increased BUN, azotemia, acidosis, hyperphosphatemia, pancreatitis, and abnormal liver function tests), have been reported for other tetracycline-class antibacterial drugs, and may occur with NUZYRA. Discontinue NUZYRA if any of these adverse reactions are suspected.

Prescribing NUZYRA in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

ADVERSE REACTIONS

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

DRUG INTERACTIONS

Patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage while taking NUZYRA.

Absorption of tetracyclines, including NUZYRA is impaired by antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate and iron containing preparations.

USE IN SPECIFIC POPULATIONS

Lactation: Breastfeeding is not recommended during treatment with NUZYRA.

Please see full Prescribing Information for NUZYRA.

References: 1. NUZYRA [Prescribing Information]. Paratek Pharmaceuticals, Inc. 2. O’Riordan W, Green S, Overcash JS, et al. Once-daily oral omadacycline versus twice-daily oral linezolid for acute bacterial skin and skin structure infections (OASIS-2): a phase 3, double-blind, multicentre, randomised, controlled, non-inferiority trial. Lancet Infect Dis. 2019;19(10):1080-1090. 3. O’Riordan W, Green S, Overcash JS, et al. Omadacycline for acute bacterial skin and skin-structure infections. N Engl J Med. 2019;380(6):528-538. 4. Cornely OA, File TM Jr, Garrity-Ryan L, et al. Safety and efficacy of omadacycline for treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections in patients with mild-to-moderate renal impairment. Int J Antimicrob Agents. 2021;57(2):106263. 5. Pai MP, Wilcox MH, Chitra S, McGovern PC. Safety and efficacy of omadacycline by BMI categories and diabetes history in two Phase III randomized studies of patients with acute bacterial skin and skin structure infections. J Antimicrob Chemother. 2021;76(5):1315-1322. 6. Stets R, Popescu M, Gonong JR, et al. Omadacycline for community-acquired bacterial pneumonia. N Engl J Med. 2019;380(6):517-527. 7. Pai MP, Wilcox M, Chitra S, McGovern P. Safety and efficacy of omadacycline by body mass index in patients with community-acquired bacterial pneumonia: subanalysis from a randomized controlled trial. Respir Med. 2021;184:106442. 8. Torres A, Garrity-Ryan L, Kirsch C, et al. Omadacycline vs moxifloxacin in adults with community-acquired bacterial pneumonia. Int J Infect Dis. 2021;104:501-509.