NUZYRA is a tetracycline class antibacterial indicated for the treatment of adult patients with the following infections caused by susceptible microorganisms ( 1 ): Community-acquired bacterial pneumonia (CABP) ( 1.1 ) Acute bacterial skin and skin structure infections (ABSSSI) ( 1.2 ) 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 bacteria.
( 1.3 )
1.1Community-Acquired Bacterial Pneumonia
NUZYRA is indicated for the treatment of adult patients with community-acquired bacterial pneumonia (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 .
1.2Acute Bacterial Skin and Skin Structure Infections
NUZYRA is indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI) caused by the following susceptible microorganisms: 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.
1.3Usage
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. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
NUZYRA is contraindicated in patients with known hypersensitivity to omadacycline or tetracycline class antibacterial drugs, or to any of the excipients [see Warnings andPrecautions (5.3) and Adverse Reactions (6.1) ]. Known hypersensitivity to omadacycline, tetracycline class antibacterial drugs or any of the excipients in NUZYRA ( 4 )
Warnings and precautions
Tooth Discoloration and Enamel Hypoplasia : 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. ( 5.1 , 8.1 , 8.4 ) Inhibition of Bone Growth: 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.
The use of NUZYRA during tooth development (last half of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of the tetracycline class drugs, but it has been observed following repeated short-term courses. Enamel hypoplasia has also been reported with tetracycline class drugs. Advise the patient of the potential risk to the fetus if NUZYRA is used during the second or third trimester of pregnancy [see Use in Specific Populations (8.1 , 8.4) ].
5.2Inhibition of Bone Growth
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. All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in premature infants given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued.
Advise the patient of the potential risk to the fetus if NUZYRA is used during the second or third trimester of pregnancy [see Use in Specific Populations (8.1 , 8.4) ] .
5.3Hypersensitivity Reactions
Hypersensitivity reactions have been reported with NUZYRA [see Adverse Reactions (6.1) ]. 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 [see Contraindications (4) ] .
Discontinue NUZYRA if an allergic reaction occurs.
5.4 Clostridioides difficile- Associated Diarrhea 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. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy.
CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated.
5.5Tetracycline Class Effects
NUZYRA is structurally similar to tetracycline class of 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.
5.6Development of Drug-Resistant Bacteria Prescribing
NUZYRA in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria [see Indications and Usage (1.3) ].
Interactions
Patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage while taking NUZYRA. ( 7.1 ) Absorption of tetracyclines, including NUZYRA, is impaired by antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate and iron containing preparations. ( 2.1 , 7.2 )
7.1Anticoagulant Drugs
Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage while also taking NUZYRA.
7.2Antacids and Iron Preparations Absorption
of oral tetracyclines, including NUZYRA, is impaired by antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate, and iron containing preparations [see Dosage and Administration (2.1) ].
Pregnancy and breastfeeding
8.1Pregnancy Risk Summary
NUZYRA, like other tetracycline class antibacterial drugs, may cause discoloration of deciduous teeth and reversible inhibition of bone growth when administered during the second and third trimester of pregnancy [see Warnings and Precautions ( 5.1 , 5.2) , Data, Use in Specific Populations ( 8.4 )]. The limited available data of NUZYRA use in pregnant women is insufficient to inform drug associated risk of major birth defects and miscarriages.
Animal studies indicate that administration of omadacycline during the period of 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 intravenous dose of 100 mg and the oral dose of 300 mg. Reductions in fetal weight occurred in rats at all administered doses (see Data ). In a fertility study, administration to rats during mating and early pregnancy resulted in embryo loss at 20 mg/kg/day; systemic exposure based on AUC was approximately equal to the clinical exposure level [see Nonclinical Toxicology ( 13.1) ] .
Results of studies in rats with omadacycline have shown tooth discoloration. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15-20%.
Data Animal Data Intravenous infusion of omadacycline to pregnant rats during organogenesis (gestation days 6-17) at doses of 5 to 80 mg/kg/day resulted in maternal lethality at 80 mg/kg/day. Increased embryo-fetal lethality and fetal malformations (whole body edema) occurred at 60 mg/kg/day (7 times the clinical AUC), dose-dependent reductions in fetal body weight occurred at all doses, and delayed skeletal ossification occurred at doses as low as 10 mg/kg/day (Systemic exposure based on AUC at a similar dose in unmated female rats in a separate study was approximately half the clinical exposure).
In pregnant rabbits, intravenous infusion of 5, 10 or 20 mg/kg/day during organogenesis (gestation days 7-18) resulted in maternal lethality and body weight loss at 20 mg/kg/day. Embryo-fetal lethality, congenital malformations of the skeleton, and reduced fetal weight also occurred at 20 mg/kg/day (7 times the clinical AUC). Cardiac and lung malformations were present in dose-related incidence at 10 and 20 mg/kg/day.
The fetal no-adverse-effect-level in the rabbit embryo-fetal development study was 5 mg/kg/day, at approximately 1.2 times the clinical steady state AUC. Intravenous infusion of omadacycline to pregnant and lactating rats at doses of 7.5, 15 and 30 mg/kg/day did not adversely affect survival, growth (other than lower pup body weights and/or gains at the high dose that were only statistically significant at sporadic intervals), postnatal development, behavior, or reproductive capability of offspring at maternal doses up to 30 mg/kg/day (approximately equivalent to 3 times the IV clinical dose of 100 mg/day, based on doses normalized for total body surface area), the highest dose tested, although dosing was discontinued early in a number of animals in this group due to injection site intolerance.
Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can have toxic effects on the developing fetus (often related to retardation of skeletal development). Evidence of embryotoxicity also has been noted in animals treated early in pregnancy.
Adverse reactions
The following clinically significant adverse reactions are described in greater detail in the Warnings and Precautions section of labeling: Tooth Development and Enamel Hypoplasia [see Warnings and Precautions (5.1) ] Inhibition of Bone Growth [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Tetracycline Class Effects [see Warnings and Precautions ( 5.5 )] ABSSSI: The most common adverse reactions (incidence ≥2%) are nausea, vomiting, infusion site reactions, alanine aminotransferase increased, aspartate aminotransferase increased, headache and diarrhea.
CABP : The most common adverse reactions (incidence ≥2%) are alanine aminotransferase increased, headache, hypertension, and aspartate aminotransferase increased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Paratek Pharmaceuticals, Inc. at 1-833-727-2835 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Overview of the Safety Evaluation of NUZYRA NUZYRA was evaluated in three Phase 3 pivotal clinical trials (Trial 1, Trial 2 and Trial 3) and one Phase 3 postmarketing clinical trial (Trial 4).
These trials included one pivotal Phase 3 trial in CABP patients (Trial 1), one Phase 3 postmarketing trial in CABP patients (Trial 4), and two pivotal Phase 3 trials in ABSSSI patients (Trial 2 and Trial 3). Across all Phase 3 trials, a total of 1409 patients were treated with NUZYRA. In Trials 2 and 3, 691 patients with ABSSSI received NUZYRA, of which 368 patients were treated with only oral NUZYRA. In Trials 1 and 4, 718 patients with CABP were treated with NUZYRA.
Clinical Trial Experience in Patients with Community-Acquired Bacterial Pneumonia Trial 1 was a Phase 3 CABP trial that enrolled 774 adult patients, 386 randomized to NUZYRA (382 received at least one dose of NUZYRA and 4 patients did not receive the study drug) and 388 randomized to moxifloxacin (all 388 received at least one dose of moxifloxacin). The mean age of patients treated with NUZYRA was 61 years (range 19 to 97 years) and 42% were greater than or equal to 65 years of age.
Overall, patients treated with NUZYRA were predominantly male (53.7%), white (92.4%), and had a mean body mass index (BMI) of 27.3 kg/m 2 . Approximately 47% of NUZYRA treated patients had CrCl <90 ml/min. Patients were administered an IV to oral switch dosage regimen of NUZYRA. The total treatment duration was 7 to 14 days. Mean duration of IV treatment was 5.7 days and mean total duration of treatment was 9.6 days in both treatment arms.
Trial 4 was a Phase 3 CABP trial that enrolled 670 adult patients, 336 randomized to NUZYRA (all 336 received at least one dose of NUZYRA) and 334 randomized to moxifloxacin (332 received at least one dose of moxifloxacin and 2 patients did not receive the study drug). The mean age of patients treated with NUZYRA was 63.3 years (range 23 to 96 years) and 47.6% were greater than or equal to 65 years of age. Overall, patients treated with NUZYRA were predominantly male (53.0%), white (99.7%), and had a mean body mass index (BMI) of 27.0 kg/m 2 .
Approximately 54% of NUZYRA treated patients had CrCl <90 ml/min. Patients were administered an IV to oral switch dosage regimen of NUZYRA. The total treatment duration was 7 to 10 days with up to 14 days allowed for patients with positive blood cultures at the Screening visit. Mean duration of IV treatment was 6.6 days and mean total duration of treatment was 9.0 days in both treatment arms. Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation In Trial 1, a total of 23/382 (6.0%) patients treated with NUZYRA and 26/388 (6.7%) patients treated with moxifloxacin experienced serious adverse reactions.
There were eight deaths (2%) in 382 patients treated with NUZYRA as compared to four deaths (1%) in 388 patients treated with moxifloxacin. Discontinuation of treatment due to any adverse reactions occurred in 21/382 (5.5%) patients treated with NUZYRA and 27/388 (7.0%) patients treated with moxifloxacin. In Trial 4, a total of 17/336 (5.1%) patients treated with NUZYRA and 15/332 (4.5%) patients treated with moxifloxacin experienced serious adverse reactions.
There were six deaths (1.8%) in each treatment group (6/336 in the NUZYRA group, and 6/332 in the moxifloxacin group). Discontinuation of treatment due to any adverse reactions occurred in 9/336 (2.7%) patients treated with NUZYRA and 9/332 (2.7%) patients treated with moxifloxacin. Most Common Adverse Reactions Table 4 lists the most common adverse reactions occurring in ≥2% of CABP patients receiving NUZYRA in Trial 1 and Trial 4.
Table 4: Adverse Reactions Occurring in ≥2% of CABP Patients Receiving NUZYRA in Pooled Trials 1 and Trial 4 Adverse Reaction NUZYRA (N = 718) Moxifloxacin (N = 720) Alanine aminotransferase increased 2.8
2.6 Headache 2.8
2.8 Hypertension 2.2
1.7 Aspartate aminotransferase increased 2.1
1.9 Clinical Trials Experience in Patients with Acute Bacterial Skin and Skin Structure Infections Trial 2 was a Phase 3 ABSSSI trial that enrolled 655 adult patients, 329 randomized to NUZYRA and 326 randomized to linezolid. Trial 3 was a Phase 3 ABSSSI trial that enrolled 735 adult patients, 368 randomized to NUZYRA and 367 randomized to linezolid. In Trial 2 (IV to oral switch trial), the mean age of patients treated with NUZYRA was 47 years (range 19 to 88).
Overall, patients treated with NUZYRA were predominantly male (62.8%), white (91.0%) and had a mean BMI of 28.1 kg/m 2 . In Trial 3 (oral only trial), the mean age of patients was 43 years (range 18 to 86). Patients treated with NUZYRA were predominantly male (65.8%), white (88.9%), and had a mean BMI of 27.9 kg/m 2 . In Trials 2 and 3, approximately 12% of NUZYRA treated patients had CrCl <90 ml/min. Overall, the mean and median calculated lesion area was similar across both trials.
Trial 2 required at least 3 days of IV treatment followed by switch to oral regimen based on physician's discretion. Mean duration of IV treatment in Trial 2 was 4 days and mean total duration of treatment was 9 days in both treatment arms. In Trial 3, only oral therapy was administered, and mean total duration of treatment was 8 days in both treatment arms. The median days on treatment in the pooled ABSSSI trials was 9 days for both NUZYRA and linezolid.
Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation In the pooled ABSSSI trials, serious adverse reactions occurred in 16/691 (2.3%) of ABSSSI patients treated with NUZYRA and 13/689 (1.9%) of patients treated with comparator. Discontinuation of treatment due to adverse events occurred in 12 (1.7%) NUZYRA treated patients, and 10 (1.5%) comparator treated patients. There was 1 death (0.1%) reported in NUZYRA treated patients and 3 deaths (0.4%) reported in linezolid patients in ABSSSI trials.
Most Common Adverse Reactions Table 5 includes the most common adverse reactions occurring in ≥2% of patients receiving NUZYRA in Trials 2 and 3. Table 5: Adverse Reactions Occurring in ≥2% of ABSSSI Patients Receiving NUZYRA in Pooled Trials 2 and 3 Adverse Reaction NUZYRA (N = 691) Linezolid (N = 689) Nausea In Trial 2, which included IV to oral dosing of NUZYRA, 40 (12%) patients experienced nausea and 17 (5%) patients experienced vomiting in NUZYRA treatment group as compared to 32 (10%) patients experienced nausea and 16 (5%) patients experienced vomiting in the comparator group.
One patient (0.3%) in the NUZYRA group discontinued treatment due to nausea and vomiting. In Trial 3, which included the oral loading dose of NUZYRA, 111 (30%) patients experienced nausea and 62 (17%) patients experienced vomiting in NUZYRA treatment group
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
OMADACYCLINE TOSYLATE EQ 100MG BASE/VIAL
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
