Nuzyra
(omadacycline)Dosage & Administration
| Infection | Loading Doses | Maintenance Dose |
|---|---|---|
| CABP | NUZYRA Injection: Day 1: 200 mg by intravenous infusion over 60 minutes OR100 mg by intravenous infusion over 30 minutes twice (2.2) OR NUZYRA Tablets: Day 1: 300 mg orally twice (2.2) | NUZYRA Injection: 100 mg by intravenous infusion over 30 minutes once daily OR NUZYRA Tablets: 300 mg orally once daily (2.2) |
| ABSSSI | NUZYRA Injection: Day 1: 200 mg by intravenous infusion over 60 minutes OR100 mg by intravenous infusion over 30 minutes twice ( 2.3)OR NUZYRA Tablets: Day 1 and Day 2: 450 mg orally once daily (2.3) | NUZYRA Injection: 100 mg by intravenous infusion over 30 minutes once daily OR NUZYRA Tablets: 300 mg orally once daily (2.3) |
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Nuzyra Prescribing Information
Community-Acquired Bacterial Pneumonia (CABP)
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.
Acute Bacterial Skin and Skin Structure Infections (ABSSSI)
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.
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. 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.
Important Administration Instructions
NUZYRA for Injection: Do NOT administer NUZYRA for injection with any solution containing multivalent cations, e.g., calcium and magnesium, through the same intravenous line [see Drug Interactions (7.2)] . Co-infusion with other medications has not been studied [see Dosage and Administration (2.5)] .
NUZYRA Tablets: Fast for at least 4 hours and then take 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 [see Drug Interactions (7.2)and Clinical Pharmacology (12.3)].
Dosage in Adults with Community-Acquired Bacterial Pneumonia (CABP)
For treatment of adults with CABP the recommended dosage regimen (loading and maintenance) of NUZYRA is described in Table 1 below.
| Loading Doses | Maintenance Dose | Treatment Duration |
|---|---|---|
| NUZYRA Injection: 200 mg by intravenous infusion over 60 minutes on day 1. OR 100 mg by intravenous infusion over 30 minutes, twice on day 1. OR | NUZYRA Injection: 100 mg by intravenous infusion over 30 minutes once daily. OR NUZYRA Tablets: 300 mg orally once daily. | 7 to 14 Days |
| NUZYRA Tablets: 300 mg orally twice on day 1. |
Dosage in Adults with Acute Bacterial Skin Structure and Skin Infections (ABSSSI)
For treatment of adults with ABSSSI, the recommended dosage regimen (loading and maintenance) of NUZYRA is described in Table 2 below.
| Loading Doses | Maintenance Dose | Treatment Duration |
|---|---|---|
| NUZYRA Injection: 200 mg by intravenous infusion over 60 minutes on day 1. OR 100 mg by intravenous infusion over 30 minutes, twice on day 1. OR | NUZYRA Injection: 100 mg by intravenous infusion over 30 minutes once daily. OR NUZYRA Tablets: 300 mg orally once daily. | 7 to 14 Days |
| NUZYRA Tablets: 450 mg orally once a day on day 1 and day 2. |
Dosage Adjustments in Patients with Renal or Hepatic Impairment
No dosage adjustment is warranted in patients with renal or hepatic impairment [see Clinical Pharmacology (12.3)].
Preparation and Administration of NUZYRA for Injection Intravenous Solution
Reconstitution and Dilution:
- NUZYRA must be reconstituted and then further diluted under aseptic conditions. To prepare the required dose for intravenous infusion, reconstitute and dilute the appropriate number of vials, as determined from Table 3 below.
- Reconstitute each 100 mg vial of NUZYRA with 5 mL of Sterile Water, 0.9% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP, for Injection.
- Gently swirl the contents and let the vial stand until the cake has completely dissolved and any foam disperses. Do not shake the vial.
- The reconstituted NUZYRA solution should be yellow to dark orange in color; if not, the solution should be discarded. Visually inspect the reconstituted NUZYRA solution for particulate matter and discoloration prior to further dilution and administration. If necessary, invert the vial to dissolve any remaining powder and swirl gently to prevent foaming.
- Immediately (within 1 hour), withdraw 5 mL or 10 mL of the reconstituted solution and further dilute to a 100 mL (nominal volume) of 0.9% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP, bag for injection. The concentration of the final diluted infusion solution will either be 1 mg/mL or 2 mg/mL in accordance with Table 3 below. Discard any unused portion of the reconstituted solution.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
| NUZYRA for Injection Dose | Number of Vials to Reconstitute for Further Dilution | Volume of Reconstituted Solution (5 mL/vial) to Withdraw for Further Dilution | Final Infusion Concentration of NUZYRA |
|---|---|---|---|
| 200 mg | 2 Vials | 10 mL | 2 mg/mL |
| 100 mg | 1 Vial | 5 mL | 1 mg/mL |
Storage of the Diluted Infusion Solution
The NUZYRA diluted infusion solution may be used within 24 hours at room temperature (less than or equal to 25°C) or within 7 days when refrigerated (2°C to 8°C). Do not freeze. Allow the infusion bag to reach room temperature prior to use.
Administration
After reconstitution and dilution, administer NUZYRA by intravenous infusion, using a total infusion time of 60 minutes for a 200 mg dose, or a total infusion time of 30 minutes for a 100 mg dose [see Dosage and Administration (2.2, 2.3)] .
Administer NUZYRA intravenously through a dedicated line or through a Y-site. If the same intravenous line is used for sequential infusion of several drugs, the line should be flushed with 0.9% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP, before and after infusion of NUZYRA. The compatibility of NUZYRA with other drugs and infusion solutions other than 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP has not been established.
NUZYRA for Injection
Each single-dose vial contains 100 mg omadacycline (equivalent to 131 mg omadacycline tosylate) which must be reconstituted and further diluted prior to intravenous infusion. The lyophilized powder is a yellow to dark orange cake.
NUZYRA Tablets
Each tablet contains 150 mg of omadacycline (equivalent to 196 mg omadacycline tosylate) in yellow, diamond-shaped, film-coated tablets debossed with OMC on one side and 150 on the other side.
Pregnancy
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 (5.2, 5.3), 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.
Lactation
Risk Summary
There is no information on the presence of omadacycline in human milk, the effects on the breastfed infant or the effects on milk production. Tetracyclines are excreted in human milk; however, the extent of absorption of tetracyclines, including omadacycline, by the breastfed infant is not known. Because there are other antibacterial drug options available to treat CABP and ABSSSI in lactating women and because of the potential for serious adverse reactions, including tooth discoloration and inhibition of bone growth, advise patients that breastfeeding is not recommended during treatment with NUZYRA and for 4 days (based on half-life) after the last dose.
Females and Males of Reproductive Potential
Contraception
Females
NUZYRA may produce embryonic or fetal harm [see Use in Specific Populations (8.1)]. Advise patients to use an acceptable form of contraception while taking NUZYRA.
Infertility
Males
In rat studies, injury to the testis and reduced sperm counts and motility occurred in male rats after treatment with omadacycline [see Nonclinical Toxicology (13.1)].
Females
In rat studies, omadacycline affected fertility parameters in female rats, resulting in reduced ovulation and increased embryonic loss at intended human exposures [see Nonclinical Toxicology (13.1)] .
Pediatric Use
Safety and effectiveness of NUZYRA in pediatric patients below the age of 18 years have not been established.
Due to the adverse effects of the tetracycline class of drugs, including NUZYRA on tooth development and bone growth, use of NUZYRA in pediatric patients less than 8 years of age is not recommended [see Warnings and Precautions (5.1, 5.2)].
Geriatric Use
Of the total number of patients who received NUZYRA in the Phase 3 clinical trials (n=1073), 200 patients were ≥65 years of age, including 92 patients who were ≥75 years of age. In Trial 1, numerically lower clinical success rates at early clinical response (ECR) timepoint for NUZYRA-treated and moxifloxacin-treated patients (75.5% and 78.7%, respectively) were observed in CABP patients ≥ 65 years of age as compared to patients <65 years of age (85.2% and 86.3%, respectively). Additionally, all deaths in the CABP trial occurred in patients >65 years of age [see Adverse Reactions (6.1)].
No significant difference in NUZYRA exposure was observed between healthy elderly subjects and younger subjects following a single 100 mg IV dose of NUZYRA [see Clinical Pharmacology (12.3)] .
Hepatic Impairment
No dose adjustment of NUZYRA is warranted in patients with mild, moderate, or severe hepatic insufficiency (Child-Pugh classes A, B, or C) [see Clinical Pharmacology (12.3)].
Renal Impairment
No dose adjustment of NUZYRA is warranted in patients with mild, moderate, or severe renal impairment, including patients with end stage renal disease who are receiving hemodialysis [see Clinical Pharmacology (12.3)].
NUZYRA is contraindicated in patients with known hypersensitivity to omadacycline or tetracycline class antibacterial drugs, or to any of the excipients [see Warnings and Precautions (5.3)and Adverse Reactions (6.1)].
Mortality Imbalance in Patients with Community-Acquired Bacterial Pneumonia
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 [see Use in Specific Populations (8.5)] . 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 [see Adverse Reactions (6.1)].
Tooth Discoloration and Enamel Hypoplasia
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)].
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. 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)] .
Hypersensitivity 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.
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.
Tetracycline 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.
Development of Drug-Resistant Bacteria
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 [see Indications and Usage (1.3)].